Low frequency vibration assisted blood perfusion emergency system

ABSTRACT

A non-invasive vibrator comprising a vibration source operable to generate vibration at a frequency in the range of 1-1000 Hz, and a phased array ultrasonic imaging transducer operatively connected to said vibration source, such as to enable targeting of vibration via an image generated on an ultrasonic display. The preferred vibrator is operable at a frequency greater than 20 Hz and an amplitude greater than 1 mm, such as to provide an effective, deeply penetrative transthoracic tool in remediation of blood flow disturbances within the thoracic cavity (such as acute myocardial infarction). In a variation, means for emitting a therapeutic low frequency ultrasonic waveform in concert with vibration in the range of 1-1000 Hz (wherein both waveforms are simultaneously directed by high frequency ultrasonic imaging) is also provided.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a divisional of U.S. patent application Ser.No. 10/902,122, filed on Jul. 30, 2004, which claims priority toCanadian Patent Application No. 2439667 A1 filed Sep. 4, 2003. Thecontents of these applications are incorporated herein by reference intheir entirety.

FIELD OF THE INVENTION

This invention relates to noninvasive medical systems for impartingtranscutaneously applied low frequency mechanical vibrational energy tothe human body, to improve first line emergency treatment of acutethrombotic vascular obstructions. More particularly, this inventionrelates to non-invasive drug delivery systems to improve delivery ofsystemically administered clot disrupting and vasodilatory medicationsto acutely obstructed blood vessels.

BACKGROUND OF THE INVENTION

Acute vascular obstructions, ischemia and infarction are common medicalconcerns. Acute Myocardial Infarction (“AMI”) subsequent to coronarythromboses in particular is one of the leading causes of death in NorthAmerica. Current first line treatment of thromboses in the acute phasewhen the patient reaches professional care is typically by intravenousintroduction of thrombolytics, or a combination of drugs such asheparin, aspirin and/or GP 2b 3a platelet inhibitors to dissolve theblood clot. Intravenous and oral nitrates may also be introduced inorder to dilate the culprit coronary or other vessel, which usually hasa degree of spasm associated.

Thrombolytic drug treatment does not, however, have a high success rate.The success of systemically delivered IV drug therapy in increasingreperfusion rates in the treatment of ST elevation AMI is discussed inthe following publications:

1.) American Heart Association, Satellite Symposium 73rd ScientificSession, St. Michael's Review, New Orleans, La.; Nov. 11, 2000.

2.) Francis W M.D., “Ultrasound-Enhanced Thrombolysis.”Echocardiography: A. Jrnl. of CV Ultrasound & Allied Tech. Vol. 18, No.3, 2001. pp 239-246.

3.) Sanborn T et al., “Impact of Thrombolysis Intra-aortic Balloon PumpCounter pulsation and their Combination in Cardiogenic ShockComplicating Acute Myocardial Infarction.”, SHOCK REGISTRY JACC, 36 (3)Suppl. A. 2000, 1123-9.

The American Heart Association, Satellite Symposium 73rd ScientificSession, St. Michael's Review reported reperfusion rates (i.e. TIMI 3flow @ 60-90 minutes) with standard thrombolytic therapy varying between50 and 63%.

Francis reported that lytic therapy fails to achieve any reperfusion (atall) in up to 20% of patients.

Success with drug based reperfusion treatment and in-hospital survivaldeclines markedly when the patient becomes hemodynamically unstable orenters cardiogenic shock, which is the leading cause of in-hospitaldeaths from M1 in North America. Sanborn et al. report 63% in-hospitalmortality despite the use of thrombolytic therapy.

In the case of ST elevation Acute Myocardial Infarction, whennoninvasive drug treatment (i.e. systemically introduced IVthrombolysis) to achieve reperfusion fails, invasive catheter basedtechniques such as Percutaneous Coronary Intervention (“PCI”) areemployed. Sometimes, PCI is chosen as a direct measure, whereby acoordination of the immediate use of lytics or other agents may be firstestablished in the field while en route to a cardiac catheterizationlaboratory where intervention can be performed. A disadvantage ofinvasive treatment for acute thrombotic obstructions (while verysuccessful) is the infrastructure required, particularly the cardiac“cathlab” requiring substantial equipment and staff. Such infrastructureis not readily accessible in hospitals world wide, and even whenavailable, there is a significant time requirement to coordinate and setup equipment and personnel. Due to the lack of immediate availability ofcathlabs, patients, often unstable, must be transported and/or wait forthe cathlab team to assemble. These difficulties result in a delay intreatment increasing myocardial necrosis, and reducing the likelihood ofa successful and timely reperfusion.

Treatment systems utilizing noninvasive vibration in the low frequencyultrasonic range (“LFUS” e.g. 20 kHz-100 kHz) have been employed as anadjunct to systemically delivered IV thrombolysis including coronarythrombolysis, in attempting to overcome these disadvantages. The LFUSwave form provides mechanical agitation via cavitation and acousticstreaming to the blood within the culprit vasculature wherein a bloodclot resides, thereby encouraging disruption of the clot and increasedpermeation of the drug into the clot to accelerate reperfusion.

LFUS to disrupt thromboses and assist thrombolysis, has however, onlyshown effectiveness in research applications (i.e. animal studies), forthe treatment of relatively superficial thromboses, where the exact,fixed location of the blood clot was already known to the investigator.LFUS wave forms (which deliver low amplitude micro displacements whichare imperceptible to a patient) offer no assurance of therapeuticultrasonic penetration to reach a blood clot within a human body in apractical application, without, for example, the establishment of aviable acoustic energy delivery window and targeting via direction of anapplication probe (i.e. as in ultrasonographic imaging), which takesintelligible application of force and angulation of the probe against apatient's skin via a skilled operator. The subsequent resultant need forhigh skill to direct a LFUS application makes such a therapy a poorcandidate for emergency cases where a skilled treatment operator wouldrarely be available. A non-directed LFUS treatment (without a skilledimaging approach) in particular, Is poorly suited towards human coronaryapplications as the human heart is a relatively deep structure, islocated variably within the thoracic cavity, and the blood clot is ahidden, moving target located beneath highly attenuating anatomicstructures such as lung, fat and dense intercostal muscle which does nottransmit ultrasound.

Thompson, T. et al in U.S. patent application No. 20020049395-2002,disclose the emergency application of a non-directed LFUS treatment inconjunction with thrombolytic therapy in response to Acute M1 in humans,wherein LFUS is delivered in a nonspecific manner to a patients skinsurface through a liquid cooling medium without intelligible placementand direction of the ultrasonic source through a confirmed ultrasonicpenetrating window. As stated this method is sub-optimal as it does notinsure adequate penetration of the therapeutic signal, and no proof isprovided that this style of technique will show a clinical benefit inhumans. Further examples of this kind of noninvasive LFUS treatment forvascular thromboses are disclosed in U.S. Pat. Nos. 6,126,619,5,713,831, 5,879,314, 6,126,619, and 6,398,772; as well as in U.S.patent application Nos. 20020082529, 20020107473, 20020072691,20020055693, 200200726690 and 20020091339.

Non-invasively delivered ultrasonic treatment systems directed byskilled medical imaging techniques to disrupt an undesirable target(including thromboses), have been disclosed in numerous articles andpublications.

Carter and Siegel in U.S. Pat. Nos. 5,509,896 and 5,695,460respectively, disclose an externally applied LFUS treatment probe placedin direct contact with a patient's skin (with optional means to enable“directing” or “focusing” of the LFUS wave form towards the area orvolume targeted) to improve emergency thrombolysis, including coronarythrombolysis. A thrombolytic agent and/or cavitating micro bubblesolution is preferably introduced by a catheter placed “proximate” thesite of the vascular obstruction, to ensure effectiveness of thetreatment system. The requirement of high skill (both in directing thetreatment probe, and in the invasive procedure of introducing acatheter) is not ideal (nor preferable) for first line therapyapplications in the field or in the emergency room. Furthermore theprobe contact will typically overheat and cause burning of the patient'sskin.

Lithotriptic style techniques such as in U.S. Pat. Nos. 5,065,741,5,207,214, 5,524,620, 5,613,940, 5,725,482, 6,068,596 and U.S. patentapplication Ser. No. 2004/0006288 A1 (which employ use of externallyimparted focused ultrasonic waves or ultrasonic shock waves directed byan imaging modality to disrupt an internal target including thromboses)have also been disclosed. This style of therapy (while common in thetreatment of kidney stones and the like) has not gained acceptance inthe emergency treatment of acute vascular obstructions or thromboticobstructions, probably because thrombotic lesions are difficult (if notimpossible) to conveniently image, and these style of applications areinexpedient for use as they require advanced training, a controlledenvironment, calculations, and specialized equipment to employ:Furthermore, lithotriptic systems and other focused wave therapytechniques are generally limited to treatment of stationary targetswithin the human body, hence applications to the coronary arteries (suchas in the acute treatment of coronary thrombotic lesions) cannotprospectively be performed.

Low frequency mechanical vibration treatment systems have beenconsidered in the invasive treatment of thrombotic obstructions viacatheter based techniques. U.S. Pat. No. 6,287,271 to Dubrul et al., forexample, discloses a low-frequency (1-1000 Hz) vibrating catheter drugdelivery system resulting in 68% lysing when placed proximally to anartificial clot in a test tube with the drug Urokinase, versus 4.5%lysing with Urokinase treatment alone. As stated above, this system isinvasive, and thereby requiring great specialized skill and equipment tointroduce a catheter directly to the thrombosis site, and thus has noutility as a first line measure in the field or in emergency room cases.

Generally non-invasively delivered low frequency vibration or percussionin the sonic to infrasonic ranges has received little focus in the fieldof treatment of acute vascular obstructions, ischemic events or bloodflow disturbances.

Cardio Pulmonary Resuscitation (“CPR”), which is essentially highdisplacement amplitude compressional wave energy of 1.5 Hz (i.e. verylow frequency vibration), was paired used successfully in conjunctionwith coronary thrombolysis in cases of known acute myocardial infarctionwhich had deteriorated and a poor outcome was otherwise imminent. Thesecases were reported by Tiffany et al. in “Bolus Thrombolytic InfusionsDuring CPR for Patients With Refractory Arrest Rhythms: Outcome of aCase Series” (Annals of Emergency Medicine, 31:1, January 1998,134-136). This medical method, which was designed to sustain the life ofthe patient conjointly with the deliverance of thrombolysis (and not toact as an adjunct to thrombolysis per se), is limited to cardiac arrestsituations, and the manual nature of the application of highdisplacement amplitude, mechanical energy by human hand would be laborintensive, potentially tiresome to an operator, and would eventuallycause undue harm to a patient if delivered for sustained periods.

Wobser, E et al. in an article “Intragastral Disintegration of BloodCoagula by Mechanical Vibration” in Endoscopy 10, 1978, 15-19; disclosesa 50-500 Hz “flexural electromagnetic resonator” for insertion into thestomach for disruption of “big blood coagula” in order to facilitateendoscopic examination in GI bleeds. Furthermore, Lee in U.S. Pat. No.5,676,637 discloses a low frequency vibratory probe for insertion in theanus to dissolve venous thromboses to improve blood circulation in thetreatment of hemorrhoids. Neither system is directed towards treatmentof acute vascular blockages or emergency blood flow disturbances, andneither instrument is configured to enable effective penetration througha significantly attenuating barrier such as the chest wall or otherexternal body surface.

Matsuura in U.S. Pat. No. 6,424,864 B1 discloses an all purpose wavetherapy system (i.e. applying electric, electromagnetic and/or acousticwaves) for treatment of a plurality of ailments ranging from depression,to rheumatism, to infertility, to poor blood circulation in the handsand feet. In one disclosed embodiment, sound waves generated through oneof a sonic platform apparatus or set of head phones enables acoustictherapy to the body (or “cuticle”, or “ears”) of a user in contact withthe apparatus. The '864 patent describes a low intensity, dissipatedtherapeutic system of acoustic and electromagnetic wave transmission toa user, and is thereby not suitable to emergency disruptive andagitative applications wherein the impartation of highly concentratedexternal percussive force to predetermined or selected application sitesis required to ensure therapeutic penetration and effectiveness.Furthermore, this system is not prescribed towards the treatment ofacute vascular obstructions or ischemic events, hence there are nomethods by which these particular applications could be performed.

Randoll in U.S. Pat. No. 6,579,251 B1 discloses a low frequencyoscillatory device for the treatment of a plurality of ailmentsincluding “micro circulation disorders”, employing a rotatingeccentrically mounted treatment head which effectively delivers (whenrotating) oscillatory skin displacements of between 4 to 7 mm at afrequency of 5-25 Hz to its user. The '251 patent mimics patient“tremors” to drive sequestered fluids through the valved systems of theveins and lymphatics to clear tissue spaces. Such rotating head devicesare not designed nor intended for the emergency treatment of acute bloodflow disturbances, and are energy inefficient as the forces of vibrationare directed tangentially to the skin surface.

Endo, Y in GB2167961 discloses a bed (or mattress) sheet with aplurality of vibrating members to be applied to the body surface of auser while sleeping, for several uses ranging from reduced “sleeplatency” to the prevention of “interruption in blood circulation”. The'961 patent Is not directed to emergency applications or response toischemic events, and the vibration disclosed is ineffectual as it is oflow amplitude and cannot be concentrated to a particular body partafflicted.

Cossone, A. et al. in PCT Appl. WO 02/0782 A2, and U.S. Pat. No.6,500,134 B1 discloses a water-bath vibrating palliative, therapeuticsystem, with an optimal frequency of 600 Hz to generally improvecoronary artery circulation in chronic cases. This water bath method isnot designed (and is impractical) for use in the field and prospectivelyfor heart attack or acute cases, and the water to skin vibrationalcoupling is energy transmission inefficient, of low amplitude, and doesnot enable focusing of treatment to key area's upon the chest wall orother body part which would confer maximum benefit.

Nagy in European Patent Appl. No. 0429109 B1 and U.S. Pat. No. 5,291,894discloses a loud speaker system operational to generate acoustic waves(i.e. sound waves through air) in the 1-1000 Hz and 20 Hz-20 kHz rangerespectively, for the chronic degenerative treatment ofvasoconstrictions resulting in poor circulation and stasis to the limbsof a patient. Nagy also names, in short, the optional use of a“piezoelectric element” which may alternatively be placed in directcontact against the body part treated. Sound waves through air are ahighly inefficient means for delivering mechanical energy to the humanbody (i.e. the forces produced to the skin surface treated would benegligible), and there is no proof provided that this style of therapywould assist blood circulation in acute or chronic cases. Similarly“piezoelectric elements” (which are generally used to emit microdisplacements in the ultrasonic ranges), are not operable toindependently generate high displacements under load (i.e. in the lowfrequency ranges), hence cannot supply (prospectively) the agitativepercussive force or mechanical energy required to ensure therapeuticpenetration and effective treatment in emergency thrombotic applicationswhich are often deeply situated.

Sackner in U.S. patent application No. 20020103454 discloses a“vibrating” “reciprocating movement platform” or bed which oscillates ina to and fro motion (i.e. in the head to foot direction), delivering“external pulses” to a human body in the frequency range of 0.25-6 Hz,for a plurality of applications including improving blood circulation inchronic and acute cases. The '454 patent application invokes hemodynamicforces or “pulses” by virtue of the accelerations and deceleration's ofthe movement platform which purportedly instill sheer stresses fromblood to endothelium of the vasculature, which is known to invoke theliberation of endogenous “beneficial mediators” such as t-PA, EDRF, andNitric Oxide (all of which are of assistance in the improvement of bloodflow and prophylaxis to disease). Whole body “vibration” methods such asSackner describes are not well suited for treatment of acute thromboticlesions or emergency blood flow disturbances as relatively small (orinsignificant) localized forces to the targeted vascular regionsthemselves are generated. Furthermore, the oscillations emitted arelower than the resonance frequency of the heart within the thoraciccavity, hence the vibratory effect to the heart (and coronaries) wouldbe even further diminished in cardiac applications. Finally thetreatment method invariably also shakes the patient's head which ispotentially dangerous and inappropriate if the treatment system whereever to be used conjointly with thrombolytic therapy.

Jap. Pat. No. JP 8,089,549 (“549”) to Koiwa and Honda discloses anoninvasive 50 Hz diastolic timed chest wall vibrator treatment systemvia a singular mechanical probe to skin coupling interface to treatcardiac ischemia. The '549 patent increases coronary blood flow tostable patients with known coronary artery narrowings, through aprescribed method of applying vibration specifically timed to thediastolic phase of the cardiac cycle via a hand held unit applied to thechest wall in a low amplitude, comfortable manner (i.e. such that thepatient “experiences no pain”). Koiwa teaches that diastolic timedvibration relaxes the myocardium (which is particularly stiff inischemic states), allowing it to perfuse more efficiently and therebyassist blood perfusion to the ischemic heart.

The '549 patent is not directed to the treatment of emergent coronaryincidents or acute thrombotic events, hence there are inherentlimitations to the disclosed system. For example, the disclosed singleprobe to skin coupling is a sub-optimal means of vibration to chest walltransmission and penetration, there is no provision for the delivery ofvibration at high amplitude to ensure therapeutic penetration (withoutfor example a skilled imaging or monitoring system), and the timedapplication of vibration limits its effectiveness as there is novibration during systole. The comfort level of the patient, and timingof vibration specific to diastole, is of lesser importance (and in factlimiting) when the key point of the therapy is to agitate and disrupt athrombus, as well as to encourage the mixing of drugs into the thrombus.Furthermore, complex monitoring and processing means via anelectrocardiographic trigger are required to effect cardiac phasecontrolled varying vibration, thus the treatment system is somewhatawkward and difficult to use prospectively in emergency cases.

Low frequency vibrators or percussive devices of high power anddisplacement enablement are well known (e.g. for massage andmobilization of pulmonary congestions), but have found no utility in thetreatment of acute vascular obstructions or response to ischemic events.These devices (such as the Mini Pro 2 Thumper™, Homedics ProfessionalPercussion Massager, and the “Deep muscle stimulator device” disclosedin U.S. Pat. No. 6,682,496), while of potential employment to thecurrent specification, are not ideal as they are equipped with one,non-adjustable high displacement amplitude setting, so their vibrationsmay be either too strong or too weak depending on the body surface andtolerance level of the patient treated. Also, such devices are known toquickly overheat and dampen oscillations when placed under load, whichgreatly diminishes their overall penetration power and application time.

Vibration devices with incrementally selectable force or power control(i.e. at a given frequency) have been generally described for a varietyof medical uses ranging from penile stimulation (U.S. Pat. No.6,027,444), gum massage (U.S. Pat. No. 3,664,331), fingertip massage(U.S. Pat. No. 2,181,282, U.S. Pat. No. 1,498,680), assisting thediffusion of hair solutions into the scalp of a user (U.S. Pat. No.5,830,177), eliminating mucus from the lung (U.S. Pat. No. 5,453,081),and for treatment of scoliosis of the spine (U.S. Pat. No. 6,082,365).These devices have not been optimally combined however, with a highpowered vibration source (i.e. one adapted to emit a high displacementamplitude while under load) and an optimized attachment interface (i.e.enabling concentrated delivery of vibration localized to a selected bodysurface), to enable an effective, penetrative vibration delivery systemsuitable for treatment of acute vascular obstructions, which are oftendeeply situated within the human body.

Harris et al. in U.S. patent application Ser. No. 2002/0161315 A1discloses a low frequency hand held percussive massager of indeterminatepower (which purportedly enables at least marginal levels of force orintensity emission control), comprising a first vibratory massageelement mounted to one side of the massage body and a pair of percussive“nodes” mounted to the opposite side. While of potential use to thecurrent specification, the disclosed massager is not ideal as theplacement and necessary operation of a vibratory element in diametricopposition to the percussive nodes is energy inefficient, and isinexpedient for use as it makes the device difficult to apply withsignificant engagement force by the hands of an operator. Furthermorethe disclosed massager does not allow for the particular selection ofvariable stroke length or waveshape control, which may be advantageousin a controlled research or clinical setting wherein definable,variable, and reproducible percussive stimuli may be desired.

High powered low frequency oscillation devices operable under load withmoduable vibratory wave forms (including selectable intensity and evenwave shape) are known to industry, but have found no common use indirect human contact for application to selected body surfaces, hencethe oscillations imparted would be either indirect and dissipated, orfundamentally unsafe to apply. Examples of such vibration sourcesconsist of: Aura Bass Shakers, Clark Synthesis Tactile SoundTransducers, industrial linear motors, speakers (i.e. voicecoils-“woofers”), and pile drivers.

There has also been little focus In the area of directing or confirmingthe penetration levels of low frequency vibration (or percussion) to aninvasively located target in a patient, via an imaging or monitoringtechnique.

Japanese Pat. No. JP 4156823 to Takishima et al. discloses aminiaturized accelerometer disposed on a transesophageal lead formonitoring penetration levels of externally imparted cardiac phasedmodulated vibration to the heart, to facilitate the diagnosis andtreatment of heart failure. The requirement of an invasive step ofintroducing a transesophageal probe to enable vibration monitoring andtargeting is not ideal (nor preferred) in emergency settings.

U.S. Pat. No. 6,068,596 to Weth et al. discloses an ultrasonic shockwave emission device coupled to an ultrasonic imaging probe to focus anddirect ultrasonic shock waves to internalized neural clusters in chronicpain management. The '596 patent is not directed towards treatment ofthromboses or acute vascular obstructions, and the resulting “pulsed”waves (which are only emitted once every couple of minutes) are in theultrasonic range hence are of low amplitude and must be focused to yielda significant internal effect. Furthermore the ultrasonic imaging probeis not utilized to emit the therapeutic ultrasonic shock waves, hence anoptimal acoustic (or penetration) delivery window through the overlyingbody surface is not established.

U.S. Pat. No. 5,919,139 to Lin discloses a low amplitude (designed for“gentle percussive hitting or vibrating”) sonic vibration source mountedside by side to an ultrasonic imaging transducer for diagnosticpurposes, which enables visualization of the invasive target vibrated.This device is not designed for therapy, and is inexpedient for use(prospectively) in the location and disruption of tissue targets, as thesonic vibration source is not advantageously placed in the same positionas the ultrasonic imaging probe upon the body surface, such as toconveniently enable an operator direct visualization and targeting ofvibration through an optimized sonic penetration window proximate thevascular target.

As can be seen from above, there is an ongoing need to optimize anoninvasive system for the treatment of vascular ischemia and infarctionby drug therapy and/or transcutaneously delivered mechanicallytherapeutic techniques. The prior art has failed to provide a simple touse, noninvasive mechanical method and apparatus that reliably ensuressufficient penetration to the culprit vessels and sites of vascularthromboses (in particular to the deeply situated vessels within thethoracic cavity such as the coronary arteries) to ensure an adequateagitative and disruptive therapeutic effect in emergency cases.Furthermore, none of the prior arts have successfully integrated asystemically delivered drug therapy system, and/or the optional use of apractical noninvasive imaging system for targeting therapy, to optimallyenable such an apparatus.

There is accordingly a need for an effective and easy to apply emergencyresponse system in the application of noninvasive, therapeuticmechanical energy to the human body for the treatment of acute vascularobstructions. The system should be optionally portable to enablereaching a victim in the field, employable with drugs, and preferablyadaptable to suit the expertise of an operator (i.e. with the optionalincorporation of a practical and convenient imaging system) whose skilllevel and experience (and thereby preferred clinical approach) may varymarkedly.

SUMMARY OF THE INVENTION

The present invention relates to a first line emergency response systemfor the treatment of acute thrombotic and/or vasospastic vascularobstructions via the noninvasive, high amplitude application of lowfrequency vibration in the 1-1000 Hz range. The emergency responsesystem optimally utilizes vibration as an adjunct to systemicallyadministered drug therapy. The present invention is based on theintuition that external, transcutaneously imparted low frequencyvibration at a high force or displacement amplitude can penetrate deeplywithin the human body and into the vasculature, without a requirement ofundue skill (or imaging techniques), and provide a mechanical disruptionof thromboses and synergistic support to systemically delivered drugtherapy to improve localized drug effectiveness.

The preferred embodiment relates to an emergency response systememploying a low frequency vibration blood perfusion apparatus designedto facilitate and improve the emergency treatment of acute ST elevationmyocardial infarction, by externally imparting high amplitude sonic toinfrasonic mechanical energy to the chest wall of a patient as anadjunct to systemically delivered thrombolytic therapy, (and/or anyother form of drug therapy). A noninvasive vibrator comprising avibration source with an attachment interface (to enhance transmissionand/or effectiveness of emitted vibration), enables high amplitude lowfrequency external vibration to optimally penetrate to the heart,without the requirement of a skilled imaging technique, and therebysynergistically facilitate the action of systemically directed drugtherapy by providing an agitative response to the culprit coronarycirculation. Agitation of the epimyocardium by vibration stimuli, andhence the coronary arteries, will improve (by way of sonic streaming,sheer forces and cavitation) the mixing of systemically introduced drugsdown an otherwise zero flow, or low flow vascular system. Mechanicallydelivered vibration further induces disruption of clots which leads toincreased permeation of drugs into the clots, and also low frequencyvibration independently results in a localized coronary vasodilatoryresponse to the culprit circulation which often has a degree of spasmassociated.

A practical emergency response system employing a high powered externallow frequency mechanical vibrator, optimally employable in conjunctionwith systemically delivered drug therapy and operational in the lowfrequency ranges (i.e. <=1000 Hz range), which is specifically designedand suited to assist the localized process of coronary thromboticdisruption and thrombolysis (and relief of coronary spasm if associated)in the particular emergency treatment of Acute Myocardial Infarction, isdisclosed.

The provided system is further adaptable to assist clot disruption andsystemically delivered drug therapy and effectiveness localized to otherbody regions experiencing an acute state of low blood perfusion, such asin acute vascular obstructions to the cerebral, pulmonary and peripheralvasculature.

A first aspect of the present invention is to provide a system and apreferred apparatus enabling an easy to impart, non-skilled basedvibration therapy, comprising the steps of placing a vibratornon-invasively (without an imaging modality) to a selected body surfacedeemed proximate to a culprit vascular obstruction, and applying lowfrequency vibration at a high force or displacement amplitude to theselected body surface, preferably as an adjunct to systemicallyadministered drug therapy.

A second aspect of the present invention (as a means to optimize thesystem), provides methods and apparatus to the incorporation ofultrasonic imaging, which enables a “skilled” operator (when available)to intelligibly direct externally imparted vibration in a relativelyeasy and portable manner towards an invasive target. As a third aspectof the present invention (and as a means of further optimizing thesystem), methods and apparatus enabling cardiac phase controlledvibration delivery is additionally provided, which may be of use incardiac applications, when or if the patient deteriorates to a state ofcardiogenic shock.

A fourth aspect of the present invention is to integrate the foregoinginto an effective emergency response system for treatment of acutevascular obstructions. The system is optionally portable to meet theneeds of first line emergency treatment in the field, employable withdrugs, and adaptable to meet the needs of differing operators withvarying levels of training and skill.

It is accordingly a general object of this present invention to define autility for externally placed, high amplitude, low frequency vibrationto the thorax of a patient, as a synergistic adjunct to systemicallydelivered drug therapy, in a cardiological treatment applicationassociated with acute myocardial infarction.

It is a further object of the present invention to provide an emergencyresponse system whereby 1-1000 Hz, (or preferably 1-120 Hz and optimally20-120 Hz compressional waves) are applied externally at high force anddisplacement amplitude to the chest wall of the patient, to act to as anadjunct to systemically introduced drug therapy in the first linetreatment of acute ST elevation myocardial infarction.

It is a further object of the present invention to provide an emergencyresponse system which is adaptable to provide externally imparted, highamplitude low frequency vibration to improve drug therapy and localizeddrug effectiveness to a variety of body regions suffering from an acute,emergent state of low blood perfusion, such as the body regions of thebrain, lung, and the periphery.

It is a further object of the present invention to provide an emergencyresponse system which is simple and easy to use, without a skillrequirement beyond what a nurse, paramedic, or even the patient (i.e. byself administration) could typically provide.

It is a further object of the present invention to provide a preferredhigher powered vibrator with a higher force and displacement amplitudepotential for vibration delivery to selected body surfaces than what hasbeen described in the prior art, in recognition that a potential degreeof overlying soft tissue injury such as a bruise or a degree of patientdiscomfort, is of small consequence relative to the gains of an improvedthrombolysis in an emergency situation to restore vessel flow to a majorinfarcting internal organ such as the heart.

It is a further object of the present invention to provide a preferredvibrator of the aforementioned type which is of a size and shape toenable hand held operation, such as to add portability, maneuverability,and ease of placement of the vibrator to varying body surfaces, as wellas a moduable or controllable means of applying engagement force by thehand or hands of an operator.

It is a further object of the present invention to provide a preferredvibrator of the aforementioned type with an amplitude regulatingmechanism, such as to enable a manual adjustment of displacementamplitude or force of vibration emitted to a tolerance level of apatient, which may be very low or very high depending on the bodysurface and constitution of the patient treated.

It is a further object of the present invention to provide a preferredvibrator of the aforementioned type which is operable to a broad rangeof selectable frequency, amplitude and wave form parameters, such toenable an effective research as well as clinical tool.

It is a further object of the present invention to provide a vibratorwith a selection of vibration/body surface attachment interfaces, suchas to accommodate a preferred method and/or skill level of an operatorin order to enhance vibration transmission and effectiveness.

It is a further object of the present invention to provide avibration/body surface attachment interface of the above type,comprising at least one contact (or contact node) adapted in size andshape to enable efficient seating within a rib space of a patient inorder to optimize vibration transmission to the chest wall and vascularstructures within the thoracic cavity.

It is a further object of the present invention to provide anvibration/body surface attachment interface of the above type,comprising a pair of contacts (or contact nodes) such as to enablecontact at a pair of application sites preferably bridging the sternumof the patient, in order to improve penetration to the mediasteinalcavity, and match the anatomic configuration of the base of the heartwherein the coronary anatomy is substantially distributed.

It is a further object of the present invention to provide avibration/body surface attachment interface of the above type,comprising a plurality greater than a pair of contacts (or contactnodes) wherein pairs of contacts are grouped together bridging anelongated support structure at adjustable levels, such as to enablecontact at a plurality of application sites (or intercostal spacelevels) preferably bridging the sternum of the patient, in order tomaximize penetration to the heart which is variably situated dependingon the anatomy of the patient.

It is a further object of the present invention to provide avibration/body surface attachment interface of the above type, which inaddition to supplying the means of transmitting low frequency vibrationfrom a vibration source to a patient, is additionally enabled to provideultrasonographic imaging such that a skilled operator (when available)may optimize penetration and target vibration to a culprit vascularregion or target area while concurrently imaging the target.

It is a further object of the present invention to provide avibration/body surface attachment interface of the above type, which inaddition to supplying the means of transmitting low frequency vibrationfrom a vibration source to a patient, is additionally enabled to emit atherapeutic low frequency ultrasonic wave form such as to provide a pairof therapeutic oscillating wave forms (i.e. low frequency vibration pluslow frequency ultrasound) in concert.

It is a further object of the present invention to provide avibration/body surface attachment interface of the above type, which isnot only enabled to transmit low frequency vibration from the vibrationsource and concurrently emit a low frequency ultrasonic treatment waveform (i.e. as above), but is additionally enabled to provideultrasonographic imaging such that an operator may optimize penetrationand target low frequency vibration and low frequency ultrasonicemissions to a culprit vascular region or target area while concurrentlyimaging the target.

It is a further object of the present invention to provide a mechanicaland adjustable engagement means to a vibrator comprising a clamp,wherein the clamp is adapted to bedside or stretcher use to hold thevibrator against a patient's body surface (such as the chest wall orback), so an operator need not hold the vibrator in place by handthroughout the course of vibration therapy.

It is a further object of the present invention to provide a mechanicaland adjustable engagement means to a vibrator comprising a belt system,wherein the belt system is adapted to encircle a patient's body part(such as the thorax) and hold the vibrator against the body surfacetreated (such as the chest wall) so an operator need not hold thevibrator by hand, and so that the patient may sit up or even ambulate.

It is a further object of the present invention to provide a vibrationmethod and apparatus for enabling cardiac phase controlled time andoptionally frequency varying vibration delivery, to enable the selectionof vibration timing algorithms designed to optimize vibration of theheart and coronary arteries. Cardiac phase controlled vibration is ofparticular importance in cases of acute myocardial infarction which havedeteriorated into cardiogenic shock, wherein vibration timed exclusivelyto the diastolic cardiac phase provides a positive inotropic effect inaddition to mechanical agitation of the heart and coronary arteries.

It is a primary object of the present invention to provide aself-contained, first line, mobile emergency response system and kit(and method of drug delivery) for treatment of acute, emergent,thrombotic and/or vasospastic vascular obstructions by trainedprofessionals (in the ambulance, before transportation, or in hospital),wherein the mobile, emergency response kit comprises: a high powered lowfrequency vibrator, a selection of interchangeable attachment interfacesincluding those enabling ultrasonic imaging and low frequency ultrasonictherapeutic emissions, a drug delivery means, at least one andpreferably a plurality of useful drugs to be delivered, and a portablecarrying case enabling storage and portability of the aforementionedmembers. Options to the mobile, emergency response kit include: anengagement means (selectable between a clamp and belt apparatus), and acardiac phase controlled vibration delivery system (to optimize thetiming of vibration delivery specifically for cardiac applications,which is of special importance in the case where the patientdeteriorates into a state of cardiogenic shock).

It is a final object of the present invention, to provide a selfcontained, portable, emergency response system and kit (and method ofdrug delivery) for outpatient community use, wherein the portableemergency response kit comprises a high powered low frequency vibrator,and preferably at least one anti-anginal drug to be delivered. Theportable emergency response kit is employable to a victim (or bystander)in the community for self (or assisted) treatment of chest painrefractory to and/or complimentary with conventional anti-anginaltherapy (e.g. nitro spray, or pill), wherein an acute coronary eventcannot be ruled out.

BRIEF DESCRIPTION OF THE DRAWINGS

The apparatus and method of the present invention will now be describedwith reference to the accompanying drawing figures, in which:

FIG. 1 is a perspective view of a supine patient receiving treatmentfrom an operator held vibrator according to the invention.

FIG. 2 is a perspective view of a supine patient receiving treatmentfrom a clamped vibrator according to the invention.

FIG. 3 is a perspective view of an attachment interface comprising abifurcated connector with a pair of support arms, each support armhaving a single contact according to the invention.

FIG. 4 is a perspective view of a variant attachment interfacecomprising a bifurcated connector having a plurality of support armsaccording to the invention.

FIG. 5 is a perspective view of a variant attachment interfacecomprising a variant connector having two pairs of support armsaccording to the invention.

FIG. 6 is a schematic diagram of the preferred vibrator and its operablecomponents according to the invention.

FIG. 7 is a schematic diagram of the variant cardiac phase controlledvibrator and its operable components according to the invention.

FIG. 8 is a graphic illustration of a variety of vibratory displacementwave forms according to the invention.

FIG. 9 is a perspective view of a variation of the vibratorincorporating ultrasonographic imaging with treatment vibration via ahand held technique according to the invention.

FIG. 10 is a perspective view of a variant ultrasonic imaging contactaccording to the invention.

FIG. 11 is a perspective view of a variation of the clamp mechanismaccording to the invention.

FIG. 12 is a perspective view of a patient in fowler's positionreceiving treatment from a belt engaged vibrator according to theinvention.

FIG. 13 is a schematic diagram of the preferred vibration method for theremediation of acute thrombotic vascular obstructions according to theinvention.

FIG. 14 is a schematic diagram of a variation to the preferred vibrationmethod employing ultrasonic imaging to direct vibration.

DETAILED DESCRIPTION

The present invention is a first line emergency response system andapparatus for pre-hospital or initial in-hospital treatment of patientsexperiencing an acute to sub-acute thrombotic vascular obstructionand/or associated vessel spasm. The emergency application of highamplitude, noninvasive, transcutaneously imparted low frequencyvibration, optimally as a synergistic adjunct to systemically delivereddrug therapy, with or without concomitant ultrasonic imaging, for lysingand vasodilating acute vascular thrombotic obstructions, relieving spasm(if associated), and thereby restoring blood perfusion is disclosed. Theinvention is particularly effective against thromboses in thethoracic/mediasteinal cavity.

Low frequency vibration shortens the onset and accelerates theeffectiveness of thrombolytics. Due to the urgency to treat heartattacks, strokes, pulmonary emboli, or acute peripheral arterialobstructions to major vessels, as cell death is directly proportional totime, it is of utmost importance to enhance the onset and accelerate theeffectiveness of the imparted drug treatment in lysing or clearingvascular obstructions. The noninvasive application of low frequencyvibration, in addition to its potential immediate availability toexpedite emergency treatment, has the further advantage of not causingundue heating of the overlying tissue superficial to the site ofvascular obstructions. Furthermore, the localized biophysical nature oflow frequency vibration treatment is advantageous in that as it is not adrug, it will not cause adverse systemic biochemical effects, which canotherwise be difficult to reverse such as hemorrhage.

The term “vibration” according to the present invention relates broadlyto a repetitive back and forth movement of an attachment interface (orvibratory contact) to be applied to or strike against (or percuss) abody surface of a patient, and should not be construed to mean, or belimited to any particular form of vibration unless otherwise specified.Furthermore, the term “continuously applied” or “continuous” vibrationrefers to vibration applied without a substantial break (or pause) incadence (i.e. in accordance with the selected frequency), regardless ofthe duty factor of the wave form emitted. For cardiac applications inparticular, “continuous” vibration refers to vibration impartedthroughout (or substantially throughout) the cardiac cycle, and not justduring the diastolic or systolic phase of the cardiac cycle.

The preferred embodiment of the emergency response system, or“Vibrinolytic Therapy”, involves the application of continuouslyapplied, noninvasive mechanical vibration at a frequency of 1-1000 Hz,preferably 20-120 Hz, and optimally 50 Hz to the chest wall as anadjunct to thrombolytic therapy in the treatment of acute myocardialinfarction (“AMI”). A maximized source output displacement amplituderanging from 1 up to 15 mm is selectively provided in the 1-120 Hzrange. Displacement amplitude control enables the adjustment ofvibration intensity to a tolerance level of a patient, which will varymarkedly depending on the constitution of the individual treated. Theemergency response system is not complicated and can be applied by aminimally trained paramedic or nurse without the need for specialskilled imaging guidance or targeting.

The emergency response system facilitates the action of drugs such as:thrombolytics (e.g. ACTIVASE™ (Alteplase), TNKase™ (Tenecteplase),RETAVASE™ (Reteplase), Abbokinase™ (Urokinase), Kabikinase™(Streptokinase with water), Streptase™ (Streptokinase with 0.9% NaClsolution), and Lanoteplase); GP 2b 3a platelet inhibitors (e.g. ReoPro™(Abciximab), AGGRASTAT™ (Tirofiban hydrochloride), and Integrelin™(Eptifibatide)); calcium channel blockers (e.g. ISOPTIN™ SR (VerapamilHCl), ADALAT™XL™ (Nifedipine), Cardizem™ (Diltiazem), and NORVASC™(Amlodipine besylate)); Nitrates (e.g. Nitroglycerine (spray, pill orpatch), isosorbide dinitrates (Isordil™ and Sorbitrate™), and Nipride™(Nitroprusside)); Oral anti-platelets (e.g. Acetylsalicylic Acid(Aspirin), Plavix™ (Clopidogrel), and TICLID™ (Ticlopidinehydrochloride)); Anti-coagulants (such as heparin, and other bloodthinning and coronary vasodilatory medication); concentrated oxygen andoxygen of ambient air. Micro bubble solutions which lower thecavitational threshold of a medium may also be considered as a furtheradjunct to the above listed pharmacological agents in conjunction withvibration therapy. Examples of micro bubble solutions include: EchoGen™(Dodecafluoropentane emulsion), Albunex™ (5% human albumin), LEVOVIST™(Galactose-Palmitic Acid ultrasound contrast agent), Air containingalbumin microcapsules (Quantison™ and Myomap™), SonoVue™(Sulfurhexafluoride) and Perfluorocarbon containing microbubbles(Perfluorocarbon exposed sonicated dextrose albumin PESDA). It should beunderstood that vibration therapy may be used to facilitate the actionof a single drug, or a plurality of any of the aforementioned drugs inany combination, according to their preferred use.

The low frequency vibration is imparted to the chest wall (or othertransthoracic body surface), and thereby by transmission to theepimyocardium of the heart and coronary arteries. The preferredembodiment (i.e. vibration adjunctive to thrombolytic therapy) isparticularly effective for the treatment of acute ST elevationmyocardial infarction. Vibration therapy can, with drug delivery, alsobe utilized for other forms of acute coronary syndromes such as Non Qwave (i.e. “Non ST elevation”) M1 or Unstable Angina where symptoms areotherwise refractory to medical management. A lower displacementamplitude may be considered for Non ST elevation coronary syndromes(e.g. to prevent bruising to the chest wall), wherein the displacementamplitude (or in a variation, force) of vibration is gradually titratedupwards until a relief of symptoms (or resolution ofelectrocardiographic evidence of ischemia) is realized.

Vibrinolytic therapy is effective as a first line medically adjunctivenoninvasive mechanical intervention to coronary thrombolysis. Duringcardiogenic shock, lytic therapy alone, especially without the immediateavailability of a cardiac cathlab, has a low rate of success, yet oftenremains the only realistic chance for reperfusion and in-hospitalsurvival in centers without the option of emergency rescue PercutaneousCoronary Intervention (“PCI”). Vibration therapy may also be employed inconjunction with a lower dosage of thrombolytic drugs, independently, orin conjunction with other forms of medications when thrombolytic therapyis either contraindicated (e.g. because of a risk of bleeding), or notprescribed (e.g. non-ST elevation M1 or unstable angina refractory toconventional medical management).

There are three primary effects of Vibrinolytic Therapy. First,thromboses or clots are disrupted as the mechanical agitation createssheer stresses due to cavitation and sonic streaming and thereby loosensor breaks apart the clot, resulting in increased fibrin binding sites,and improved lytic penetration. Second, sonic streaming (unidirectionalmotion of fluid in a vibration field) and convection currents aid thediffusion process and promote mixing of intravenous drugs from thesystemic circulation to the occluded, zero flow culprit vessel. Third,coronary vasodilatation within the culprit circulation is achieved asthe smooth muscle within the thrombosed, often spasming coronary arterywall is relaxed by vibration (due to a vibration induced decoupling ofthe actin-myosin filaments of the sarcomere). Secondary therapeuticeffects include a localized endogenous release of tissue plasminogenactivator, an improved left ventricular (“LV”) myocardial relaxationwith a lowering of LV diastolic pressures (and thus potentialimprovements to diastolic, transmural coronary flow), the potential fora positive inotropic effect (leading to an increased lytic filtrationpressure which is particularly useful in cardiogenic shock cases), thepotential for decreased myocardial oxygen demand for equalcontractility, and an improvement of lung/gas oxygen exchange (toprovide additional oxygen to the heart and help relieve ischemicburden).

Referring to FIG. 1, a patient 20 undergoing Vibrinolytic Therapyaccording to the preferred embodiment is shown (IVs, drugs, nasal prongsand monitoring equipment etc. not shown). The preferred engagementmeans, the hands of an operator, for applying low-frequency vibration tothe patient 20 is shown. Treatment begins with the administration of IVsystemic thrombolytic therapy, plus any other helpful drug which isdesigned to effect clot dissolution and/or vasodilate the culpritcoronary vessel. Thrombolytics may be continuously administeredintravenously, and/or by bolus as prescribed by the physician. Thecontacts 12 of the preferred vibrator 10 are placed at the treatmentsite upon the chest wall of the patient 20, and vibration at highdisplacement amplitude (preferably the highest tolerable and judged safeto patient 20) is initiated. Vibration is preferably administered oncedrug therapy has been established, however may alternatively beinitiated before or concurrent with the administration of drug therapy.

In acute myocardial infarction cases treated in an Emergency Room,preparation of the patient 20 should include sedation in similar mannerto that of a cardiac cathlab PCI treatment where the patient is expectedto remain flat (preferably supine) and relatively still for a period oftime despite an anticipated uncomfortable procedure. The recommendedapplication time is half an hour to an hour, or until clinical signs ofreperfusion become manifest. An intravenous line is established forintroduction of thrombolytic therapy, and any other IV therapy.Sedatives and anti-nausea medication and a foley catheter may beadministered to avoid interruptions of treatment. A superficialadministration of lidocaine to the skin of the chest wall applicationsite may be considered. Oxygen should be administered to assistbreathing. Intubation may be required with congestive heart failurecases in order to maintain oxygen saturation and patient positioning ina near supine position. When treatment commences in the field (as in anambulance en route to hospital) a less extravagant preparation may beconsidered, and simply reclining a patient onto a stretcher with theestablishment of an intravenous line would suffice in most situations.

For use of vibrator 10, the patient 20 is preferably placed supine,although two pillows behind the head may be allowable when the patient20 is short of breath.

Referring to FIG. 2, a variant means of engagement of vibrator 10comprising clamp 100 is shown. The base (not shown) of clamp 100 isplaced under the back or under the mattress of patient 20. Vertical bar106 extends substantially vertically from the base. Horizontal arm 108is slide-ably (i.e. in the vertical direction) and rotatably (i.e. inthe horizontal plane) attached to bar 106 and extends at substantially90 degrees from bar 106, whereby arm 108 will overhang the torso ofpatient 20. Horizontal arm 108 is lockable to vertical bar 106 bylocking knob 107, or other suitable means. Vibrator 10 is attached toarm 108 via slide-able sleeve 116. Sleeve 116 is advantageously of arectangular box shape, and is horizontally slide-able and disposed inthe horizontal direction along arm 108. Sleeve 116 contains a central,threaded, vertical hole defining an internal threaded screw column (notshown), with a matching engagement screw 110 disposed and attachedwithin the screw column. Sleeve 116 further includes locking knob 109,which tightens to lock vibrator 10 in place along arm 108. Vibrator 10is selectively lowered and raised with engagement screw 110, which hasthreads that engage the interior surface of the threaded screw column.The lower or active end of engagement screw 110 removably attaches thenon-active end of housing 14 of vibrator 10. Set screw 119 is mountedhorizontally through the top portion of sleeve 116 and abuts engagementscrew 110 thereby locking it in place during operation. A rotatablecircular piece 118 disposed at the surface within the non-active end ofhousing 14 is provided such that housing 14 may remain stationary whileengagement screw 110 adjusts vibrator 10 up or down. Inertial weight 114is optionally added to arm 108 to dampen the movement of arm 108 duringtreatment. Clamp 100 engagement is advantageous as it frees an operatorto perform other useful tasks.

The shaft 16 of vibrator 10 extends from the lower or active end ofhousing 14. A cross-shaped bifurcated connector 13 with a pair ofbifurcated support arms (described later) is remove-ably attached toshaft 16. A pair of contacts 12, advantageously of silicone rubber, areattached to the support arms of bifurcated connector 13, and provide theattachment interface with the patient 20. The preferred placement ofcontacts 12 (i.e. the default placement) is the fourth intercostalspace, about 2 cm anatomically rightward and leftward to the sternalmargins (i.e. so the medial edge of each contact 12 is roughly 2 cmlateral to the sternal margins).

Alternatively, bifurcated connector 13 is oriented obliquely to thesternum of the patient 20 such that the contacts 12 are placed to theanatomic left fourth intercostal space and anatomic right fifthintercostal space, or as a further alternate, the anatomic left thirdintercostal space and anatomic right fourth intercostal space in orderto better localize the source of vibration therapy to the plane of thebase of the heart wherein the coronary arteries arise from the aorta,and are therein substantially distributed.

As an alternate for patient 20 positioning, patient 20 may be rolledover into the prone position, wherein contacts 12 of the vibrator 10 areplaced to bridge the spine of patient 20 at the thoracic level. Thisoffers a much more comfortable application to the patient 20 (which isof special importance in the case that patient 20 cannot tolerate highintensity concentrated forces to the chest wall), and a higherdisplacement amplitude vibration with a higher engagement force (i.e.force applied by the operator to vibrator 10 against the body surfacetreated-discussed later) may be selected. This position, as it is morestable and comfortable to the patient 20, is more particularly suited toclamp 100 engagement, which (as stated) advantageously frees theoperator.

Referring to FIG. 3, the preferred attachment interface according to thepreferred embodiment of bifurcated connector 13 is shown. Bifurcatedconnector 13 is comprised of a cross shaped base consisting of a pair ofsupport arms 22, with a substantially columnar support structure 24oriented at 90 degrees to support arms 22, and an upper vertical member15, into which shaft 16 is inserted and is retained by means offriction, (or optionally any other known attachment means). Supportstructure 24 is not essential, but is preferred to enable the additionof further paired support arms 22 (and further contacts 12) at thediscretion of an operator (described later). Bifurcated connector 13 isremovably attached to shaft 16 of vibrator 10. As an option, bifurcatedconnector 13 may be fixed in place to shaft 16 of vibrator 10. Theoperator slides contacts 12 along support arms 22, so as to accommodatevarious chest wall sizes and sternum sizes. Each contact 12 is attachedto sleeve 25 with locking screw 21, placed slide-ably and lock-ably uponeach support arm 22 of bifurcated connector 13. Each sleeve 25 disposesa contact 12, wherein each contact 12 is removable to each sleeve 25 bya screw mechanism (not shown). Optionally, the spacing between contacts12 may be made electronically adjustable by means of an operatoradjustment control.

The choice of attachment interface and resultant number of contacts 12utilized comprises a risk/benefit decision where the risk is patientbruising and the benefit is superior chest wall penetration of vibrationthereby improving thrombolysis. The use of more contacts 12 willpotentially result in relatively more bruising.

In reference to FIG. 4, a variant means of chest wall attachmentcomprises the bifurcated connector 13, wherein support structure 24 isutilized to receive a pair of slide able sleeves 23, each sleeve 23comprising an additional pair of support arms 22 to enable theattachment of up to three pairs of contacts 12 to preferably bridge thesternum at the level of multiple intercostal space levels, namely the3rd, 4th and 5th intercostal space. Sleeves 23 are lockable to supportstructure 24 by locking screws 26.

To even further optimize the treatment, a further contact 12 with sleeve25 (not shown) is optionally placed more laterally on at least one ofthe anatomically leftward oriented support arms 22 at the discretion ofan operator, in order to enable application to the left mid clavicularline of the patient 20. This particular arrangement enables improvedpenetration to the mid Left Anterior Descending Artery in Acute AnteriorMich.

In further reference to FIG. 4, a modified chest wall attachment ofbifurcated connector 13 (with additional two pairs of support arms 22)may optionally be utilized to provide attachment for contacts 12 to theanatomic left 3rd, 4th and 5th intercostal spaces along the anatomicleft sternal border and anatomic left mid-clavicular line. This isaccomplished by simply moving vibrator 10 (and thereby bifurcatedconnector 13 with additional two pairs of support arms 22) to theanatomic left of patient 20, such that the contacts 12 seat against theleft sternal margin as well as within the left mid-clavicular line (i.e.as opposed to bridging the sternum). This modified chest wall attachmentoptimizes therapy directed specifically to the Left Anterior DescendingArtery (“LAD”), where the diagnosis of acute anterior myocardialinfarction has been made and the LAD, or any significant, large,leftward, coronary vessel is presumed the culprit. Alternatively,separate engagement means and a second vibration device (not shown)running preferably in phase (i.e. to avoid destructive interference ofthe vibratory signal) with pre-established vibrator 10 (or equivalent),may be utilized to provide additional therapy along the anatomical leftmid-clavicular line and thereby the LAD distribution of the patient 20.It should be noted that vibration therapy may be contraindicated to theleft 5th intercostal space (and lower intercostal spaces) at the levelspanning the mid-clavicular line to the lateral margin of the chest wallof the patient 20 (i.e. approximating the apical window in standard 2Dechocardiography), due to the remote possibility of intra-ventricular,apical early clot formation. While intra-ventricular thrombus formationis not generally considered a significant risk factor in the hyper-acutephase of an evolving acute myocardial infarction (i.e. period of timewhere thrombolytics are given), caution is warranted in certain cases.Such cases include patients who present “late” and who have thedevelopment of significant Q waves to the precordium on their initial 12lead ECG. In these cases (and in reference again to FIG. 4) the contact12 of the support arm 22 which is otherwise directed to the 5thintercostal space of the mid-clavicular line may be removed.Alternatively, an expedited 2D echocardiographic inspection of the apexof the heart of the patient 20 to rule out early clot formation (goodImages supplying apical endocardial resolution in a non-foreshortenedview as judged by an experienced echocardiographer must be obtained)would identify a low-risk group and thereby vibration therapy to theapex may commence as per the judgment of the attending clinician.

As a further option for thoracic cavity placement, (again when highintensity vibration is not tolerated to the chest wall of the patient20), bifurcated connector 13 with additional two pairs of support arms22 may be placed to bridge the spine of the patient 20, at a transverselevel equating to approximately the 3rd, 4th and 5th intercostal spaceof the anterior chest wall, with the patient 20 reclined in the proneposition.

In reference to FIG. 5, a variant connector 19 comprising upper verticalmember 15 (adapted for removable attachment to shaft 16 of the vibrator10), and a variant base consisting of support structure 24 (inisolation) adapted to receive a pair of slide-able variant sleeves 27 isshown. Each variant sleeve 27 incorporates a medially locatedsemicircular notch, and a pair of support arms 22 to enable theattachment of two pairs of contacts 12 in total (i.e. one contact 12disposed on each support arm 22). This configuration enables thebridging of the sternum of the patient 20 via two pairs of applicationsites (i.e. via a total of four contacts 12) at the level of a pair ofintercostal space levels, preferably the 3rd and 4th intercostal space.Alternatively, variant connector 19 may be placed such as to bridge thesternum at the 4th and 5th, or 3rd and 5th intercostal space level, andin yet a further variation, variant connector 19 may be placed obliquelyacross the sternum wherein the anatomically leftward oriented contacts12 are placed one intercostal space higher (or superior), to theanatomically rightward oriented contacts 12 (i.e. such as to match theconfiguration of the base of the heart, as described earlier). The uppervertical member 15 (or optionally any other known attachment means) isdisposed centrally and at a right angle to support structure 24 andpreferably maintained equidistantly between slide able variant sleeves27 (and thereby between the adjacent pair of supports arms 22), in orderto enable a balanced configuration of attachment to the patient 20. Thespacing between variant sleeves 27 (and thereby opposing support arms 22and contacts 12) are slide-ably adjustable along support structure 24(i.e. in a “longitudinal” direction, head to foot relative to thepatient 20), and the spacing between contacts 12 is also adjustablealong support arms 22 (i.e. in a “lateral” direction, side by side withrespect to the patient 20). Optionally, the spacing between variantsleeves 27 (in the “longitudinal” direction) and contacts 12 (in the“lateral” direction) may be made electronically adjustable by means ofan operator adjustment control.

To reduce the risk of bruising, the preferred bifurcated connector 13giving rise to a pair of contacts 12 (as described) may be chosen.

Alternatively, to further minimize the extent of chest wall bruising tothe patient 20, a solitary contact 12, attached to a variant,non-bifurcated connector (not shown), may be used. Solitary contact 12may be located over a solitary target site on the patient 20 which bydefault is the 4th intercostal space, with the placement of the medialedge of the solitary contact 12 preferably about 2 cm anatomicallyleftward and lateral to the left sternal margin. In a further variation,the solitary contact 12 may be adapted to be placed by friction (or anyother known attachment means) directly upon shaft 16 of the vibrator 10without the use of variant, non-bifurcated connector (or otherconnecting means).

This variant technique (i.e. use of solitary contact 12), may beutilized, regardless of bleeding and or bruising risks, in the specialcases of Anterior, Antero-Septal, or Antero-Lateral AMI, where theleftward coronary circulation is presumed the culprit and wherebysolitary contact 12 is placed anatomically leftward to the sternum ofthe patient 20. To improve efficiency and penetration of this varianttechnique, the patient 20 may be rotated from the supine position ontohis or her left side (e.g. between about 20 and 90 degrees from theplane of the bed) and supported for example by pillows or a wedge, asthis position drops the heart and left coronary circulation furtherleftward from under the sternum bringing the culprit vessels (i.e. theLeft Main, Left Anterior Descending and Left Circumflex) in closerproximity to solitary contact 12 which has been placed leftward thesternum. In the case of clamp 100 engagement, to maintain correctorientation and a perpendicular alignment between solitary contact 12and the chest wall of the patient 20 (i.e. wherein patient 20 is notlying perfectly supine), a rotating, pivoting and locking universaljoint (not shown) may be incorporated at the juncture of the loweraspect of engagement screw 110 and rotatable circular piece 118 of thenon-active end of housing 14 of the vibrator 10. In these cases thepatient 20 should preferably be only partially rotated onto his or herleft side (i.e. up to about 20 degrees from the plane of the bed) suchas to maintain structural stability of clamp 100 engagement.Alternatively (and preferably) the hand engagement, or a belt engagement(described later) may be utilized.

Next, the vibrator 10 is turned on, (preferably at a low displacementamplitude level such as 2 mm) and the contact or contacts 12 are placedagainst the target site (or sites) on the patient 20.

In an attempt to more exactingly position the contact or contacts 12 inrelation to the heart, the attending physician, nurse or paramedic mayfirst confirm or optimize a choice of a single selected intercostalspace, chosen from the anatomically leftward 3rd, 4th or 5th intercostalspace, using a stethoscope wherein relative loudness of heart soundssuggest anatomical location of the heart, as well as optimal sonictransmissibility through the chest wall. The pair of contacts 12(comprising the preferred attachment means) should be placed to eitherside of the sternum, with the anatomically leftward oriented contact 12placed upon the determined intercostal space as judged by thestethoscope method. The anatomically rightward oriented contact 12should be placed either perpendicularly across the sternum at the levelof the chosen “optimal” intercostal space, or obliquely across thesternum whereby the anatomic rightward placement of the contact 12 isplaced one intercostal space lower (or inferior) to the anatomicleftward placement of the contact 12. The sternal margin (i.e. so themedial edge of the contacts 12 are applied directly over the sternalmargin) may be considered for large breasted women. The heart soundsshould be inspected along the anatomic left sternal margin, so as toidentify the optimal leftward intercostal space. As an alternative meansof attachment, solitary contact 12 may be placed anatomically leftwardto the sternum at the determined optimal intercostal space chosen by theoperator according to the stethoscope method. Relative loudness andsustain ability of heart sounds during gently held inspiration shouldpreferably be evaluated by the operator (the louder the better) whenjudging the quality of a sonic treatment window and also inspecting forheart location which is known to vary markedly depending on theindividual treated. The target intercostal space wherein heart soundsare best heard is then marked with ink (or crayon, or felt, or any othermarker), and the anatomically leftward oriented (or solitary) contact 12of the vibrator 10 is placed in proximity to the mark.

In a further alternative method to minimize bruising and to establishoptimal transmission to the heart, vibration therapy may be provided inconjunction with high frequency, diagnostic ultrasonography (i.e. “HFUS”around 1-7 MHz), in order to optimize placement of the contact orcontacts 12 of the vibrator 10 to the chest wall of the patient 20. Toconfirm the ideal placement of the low frequency treatment vibrationsource, a trained HFUS operator (such as a Cardiac UltrasoundTechnologist, or echo trained Cardiologist for example) must firstlocate the ideal parastemal sonic penetration window viaultrasonographic techniques, wherein the preferred sonic window providesa clear visualization of the mid to basal aspect of the heart, (ideallydepicting the basal aspect of the akinetic or hypo kinetic myocardialwall which represents by anatomic reference where the culprit thrombusis most likely to reside). The imaging probe is preferably maintained ina near perpendicular orientation relative to the surface of the chestwall interrogated. The attachment variation comprising solitary contact12 is preferable in these cases to minimize overall chest wall trauma,and focus the intensity of the therapeutic vibration over the optimizedplacement site comprising the determined sonic penetration window.Optionally the otherwise preferred pair of contacts 12 may be placed toeither side of the sternum, with the anatomically leftward orientedcontact 12 placed upon the determined sonic penetration window, and theopposing anatomically rightward contact 12 placed either perpendicularlyacross the sternum at the same intercostal space level, or oneintercostal space lower (or inferior) to the leftward oriented contact12. The operator employs a conventional two-dimensional ultrasounddevice (not shown), so as to mark the determined sonic penetrationwindow on the chest (e.g. with a pen or felt marker) and place andoptionally angle the chosen attachment interface of the treatmentvibrator 10 accordingly. As stated the sonographer should preferably(while imaging) hold the imaging probe substantially perpendicular tothe chest surface (i.e. ideally less than a 20 to 30 degree angulationfrom the normal to the chest wall) such as to ensure a sonic penetrationwindow which is proximate the target area, and which is also consistentwith an anticipated perpendicular, or near perpendicular attachment ofthe contact or contacts 12 of the low frequency treatment vibrator 10.Pathologies such as COPD, with increased lung size and thereforeinterference with ultrasound, may indicate the use of differentintercostal spaces (i.e. such as the 5th intercostal space) to establishthe optimal sonic penetration window. Attachment means can be by hand,clamp 100 or a variety of engagement garments (which are describedlater). The parastemal chest wall is preferred but other sonic windowsmay be utilized (note that the apical window should be used judiciouslyas per the methodology as stated earlier).

In a further variation of the above HFUS imaging method, a “dualfunction”, simultaneous vibration and imaging system may be employed viaa single combined imaging/treatment probe (described in detail later).In this variation to the preferred embodiment, low frequency vibrationtherapy is advantageously employed in conjunction with high frequencyultrasonography (i.e. HFUS), where both high and low frequency waveforms are applied simultaneously (i.e. in real time) via a singleinstrument, which comprises an ultrasonic imaging transducer operativelyconnected (or acoustically coupled) to the active end of a low frequencyvibration source operational in the 1-1000 Hz range. The ultrasoundimaging transducer acts in this case as a variant attachment interface(or contact) to the patient 20, thereby enabling the transmission of lowfrequency vibration from the vibration source, while concurrentlyenabling ultrasonic imaging to direct vibration, at the discretion of anoperator. The method of the dual function system comprises the placementof the imaging/treatment probe (with the accompaniment of ultrasonicconduction gel) to the skin of the patient 20, such as to establish asonic penetration window depicting a target of low frequency vibration(such as the base of heart in AMI cases, as described earlier). Once asonic penetration window is established, low frequency vibration isinitiated and transmitted through the ultrasound imaging transducerattachment interface (preferably as an adjunct to drug therapy), and theapplication site is additionally maintained through continued monitoringof the ultrasonic image provided. In this manner, intelligible anatomicplacement and angulation of the imaging/treatment probe is achieved,thereby optimizing the delivery of low frequency vibration therapy tothe culprit vascular region targeted.

Optimally in still a further variation, low frequency ultrasonictreatment (LFUS) is also used in combination with HFUS imaging and lowfrequency treatment vibration in the 1-1000 Hz range, via a“multifunction system” employing a single variant LFUS enabledimaging/treatment probe (not shown and described later). In thisvariation to the preferred embodiment, low frequency vibration therapyis employed in conjunction with high frequency ultrasonography (i.e.HFUS) and “treatment” low frequency ultrasound (i.e. LFUS)simultaneously and in real time, where all three wave forms are appliedin concert via a single transmission instrument. In this manner, directHFUS imaging and targeting may be combined with low frequency vibrationin the 1-1000 Hz range, and low frequency ultrasonic energy (at around20-100 kHz, preferably 27 kHz), to optimally agitate and disrupt theculprit vascular region targeted.

The use of a combined imaging/treatment probe, (or “single transmissioninstrument”), regardless of employment of the “dual function” or“multifunction” system, at least initially involves a skilled imagingtechnique to direct vibration therapy to the ideal sonic penetrationwindow. The use of both hands to support and maintain theimaging/treatment probe with enough engagement force to the chest wall(or other body part) is suggested, or the operator can alternatively,use one hand, or utilize any of the suggested engagement means accordingto the present invention, as long as the appropriate sonic penetrationwindow is visually monitored and maintained. An inertial weight may beplaced to the backside (or optionally within the housing) of the chosen“transmission instrument” adding inertia to the apparatus and therebyassisting the operator ergonomically who may hold the transmissioninstrument in position by hand. While the supine position for thepatient is generally preferred, different patient positioning (e.g. withthe patient lying to some degree on his or her left side, up to the leftlateral debecutis position) could be utilized as per the judgment of theoperator, in order to establish the highest quality and most stablesonic penetration window available. The parasternal windows remain thepreferred application site if available (i.e. in coronary applications),however other sonic windows may be considered (note that the apicalwindow should be used judiciously as per the methodology as statedabove). Duty factor and intensity level may be selected with respect tothe LFUS application (i.e. in the multifunction system), such as toprovide the means to avoid undue heating to the skin surface of thepatient 20. Alternatively, a wet cool cloth applied intermittently tothe skin surface, and/or a periodic change of application site (or eventransmission instrument), may be utilized to prevent skin burning of thepatient 20 during joint LFUS use.

The next step in the preferred treatment method is to apply appropriateengagement force to the chest wall of the patient 20 with the vibrator10. The attending clinician applies force to the vibrator 10 against thetarget area by hand, or alternatively via rotation of engagement screw110 of clamp 100. A relatively constant, firm engagement force of atleast 5-10 N, preferably 20-100 N, and optimally 50-100 N, (measurableat shaft 16 of the vibrator 10 during operation), should be obtainedaccording to the tolerance and safety of the patient 20. In the case ofclamp 100 engagement, engagement force should preferably be firstestablished during gentle held expiration of the patient 20. Theengagement force should preferably not exceed 100 N, such as to avoidpossible dampening of oscillations of the vibrator 10. A force meter(discussed later and not shown) is optionally utilized to confirmengagement force. For clamp 100 engagement, the placement of the base ofclamp 100 (described later) under the mattress of the patient 20, may beadvantageous in some cases, in that the mattress provides for a slightdecompression when the patient 20 inhales, so as to limit the maximumengagement force on inspiration and make for a more comfortableapplication to the patent 20. In the preferred case where the vibrator10 is engaged by the hand or hands of an operator, the engagement forcecan be monitored and maintained at a near constant level, as well asmodulated as per the needs (or tolerance levels) of the patient 20.Referring back to FIG. 1, housing 14 of the vibrator 10 isadvantageously “L” shaped, incorporating a handle to facilitate handheld operation. Activation of the vibrator 10 preferably precedesengagement, however alternatively the vibrator 10 may be activated afterengagement to the patient 20, at the discretion of an operator.

As a rule of thumb, the engagement force should be the maximum force,which is tolerable for the patient 20, and will not cause the vibrator10 to significantly dampen (or stop) its oscillations. Satisfactoryengagement is further identified once the patient 20 identifies a“fluttering” in the teeth or jaw (or exhibits an undulation in thevoice) which indicates efficient transmission. It should be noted thatpatient comfort can be greatly improved by moving the application sitesabout, even slightly within the rib spaces, or alternatively todiffering rib spaces (in keeping to the selection of methods previouslydescribed). Once engaged satisfactorily (i.e. in the case of clamp 100engagement), the operator tightens set-screw 119 to lock engagementscrew 110 in place.

Vibration therapy preferably commences with selection of the maximumdisplacement amplitude or force judged safe and tolerable applied foremergency situations. This maximal setting, may result in bruising tothe chest wall (or other body surface treated), and an informed consentshould preferably be signed by the patient 20 if feasible.

It should be understood that the exact order (or selection of steps) inthe application of engagement force vs. displacement amplitude level ofthe vibrator 10 against the body surface of the patient 20 is notcritical, as long as the end result (i.e. for vibration therapy) is thata firm engagement force (i.e. at least 5-10 N. and preferably within therange of 20-100 N) at a high displacement amplitude (i.e. greater than 2mm, and preferably in the range of at least 4-15 mm, and ideallymaximized to patient 20 tolerance) is ultimately established.

If displacement amplitudes of less than or equal to about 2 mm, and/orengagement forces of less than approximately 10 N are not tolerated tothe chest wall of the patient 20 (even in the special case wherelidocaine is administered to the chest wall surface), then patient 20may optionally be placed in the prone position (not shown) and thecontacts 12 may be placed to bridge the spine of patient 20 In the upperthoracic region. Vibration at higher displacement amplitudes (oftentolerable to about 15 mm), and higher engagement forces (often tolerableto 100 N or greater), may be safely utilized in the majority of thesecases, to ensure and maximize penetration to the mediasteinal cavity andenhance clinical effectiveness of vibration.

Tests by the applicant have shown that low frequency vibrationpenetration through soft tissue is related to the applied displacementamplitude and engagement force of the vibration contact to the bodysurface vibrated. It has been ascertained that the desired engagementforce of a vibration source placed against the chest wall of the patient20 is preferably at least 5-10 N, and optimally greater than 20 N, andup to 100 N (when tolerated), to confer ideal penetration. Whenvibration is applied to the muscle groups adjacent to the spine of thepatient 20 (as an alternative means of transthoracic vibration to themediasteinal cavity), optimal engagement force is much higher (i.e.greater than 100 N may be utilized), as the application is far bettertolerated by the patient 20, and higher engagement force anddisplacement amplitudes are generally required to achieve therapeuticlevels of mediasteinal cavity penetration. Optimal displacementamplitudes also vary significantly with the constitution and tolerancelevels of the patient 20, as well as the selected body surface treated.Vibration displacement amplitudes of greater than 2 mm (and preferablyin the range of at least about 4 mm-12 mm), are preferred for chest wallapplications, and displacement amplitudes of at least about 6 mm-15 mmare preferred for transthoracic applications from the backside of thepatient 20. In the case where ultrasonic (HFUS) imaging is employed todirect or target vibration therapy, penetration to the heart isgenerally increased, and higher amplitudes and engagement forces ofvibration (i.e. which may cause bruising to the skin surface vibratedand patient 20 discomfort) are not absolutely required. Still however(regardless of the use of HFUS enabled directed therapy), the highestpossible combination of engagement force and displacement amplitude isstill recommended to yield best results in emergency treatment of acutethrombotic vascular obstructions.

In the case that the patient 20 is unable to tolerate even modest levelsof vibration (i.e. both displacement amplitude and engagement force,regardless of body surface vibrated), then a gentle applicationutilizing the weight of the vibrator 10 (or at the least 5 newtons ofengagement force) and the maximum low level of displacement amplitudetolerable to patient 20 should be utilized. Displacement amplitudes of1-2 mm (or even less, e.g. 0.1-1.0 mm-accomplished through dampeningvibration through a cushion for example) may be used in these cases.

The frequency range employed is between 1-1000 Hz, preferably between20-120 Hz, and optimally 50 Hz. It is preferable to match the resonancefrequency of the heart, which falls within a 20-120 Hz range. The heart,receiving vibration stimulus at or near its resonance frequency willvibrate with the highest possible displacement amplitudes at thelocalized areas which best receive the signal. External vibration at theresonance frequency enables transmission of the vibration signalinternally throughout the ventricular chambers with highest efficiency,thereby vibrating the entire heart and effecting optimal intraventricular transmissibility. Optimal intra ventricular transmissibilityaids agitation of the entire coronary tree, including those parts of thetree hidden behind lung or soft tissue which are poor transmitters ofvibration and therefore otherwise difficult to penetrate directly withsonic mechanical energy. The preferred frequency for chest wallvibration is a 50 Hz sinusoidal compressional wave, owing to thiswave-forms known superior chest wall penetration, intra-ventriculartransmissibility, lytic penetration, clot disruption, and arterialvasodilatation characteristics.

Higher frequencies (i.e. 150-1000 Hz), or even in the sub-ultrasonic toultrasonic range (i.e. 1000 Hz-100 kHz), while optional for clotdisruption and improved drug action to sites of thromboses, aregenerally higher than the resonance frequency of the heart and hence notreadily transmissible to all areas of the coronary anatomy by intraventricular transverse transmission means. Higher frequency vibrationalso requires diminished displacement amplitude for safe clinical use,which is a further limitation to this wave-form's potential penetratingand agitative power (i.e. through the chest wall or other body parttreated). A directed approach through an identifiable sonic penetrationwindow to ensure adequate penetration to target areas by the much weaker(i.e. lower displacement amplitude-in the low millimeter to submillimeter ranges) signal is strongly recommended for frequenciesgreater than 150 Hz, again at the highest amplitudes and forces judgedtolerable to a patient in emergency situations. Concomitant simultaneoushigh frequency ultrasound imaging (i.e. HFUS) in conjunction with lowerdisplacement amplitude vibration therapy at frequencies of greater than150 Hz, to target and direct a sonic penetration pathway to culpritareas (as per the dual function system described earlier), is theoptimal method of employment for such higher vibration treatmentfrequencies.

Generally, a range of frequencies selectively chosen between 1-1000 Hz,with the selection of multiple displacement wave-forms is disclosed. Thepresent invention provides a broad range of frequencies and wave-formswhich are advantageous, as the apparatus and system is optionallyemployed both as a treatment system and a research tool.

Treatment continues during and/or post the administration of preferreddrug agent(s) wherein stated agents may be selected solely or in anycombination from the group of thrombolytics, GP 2b 3a plateletinhibitors, anticoagulants, oral anti-platelets, vasodilators,cavitating micro bubble solutions, concentrated oxygen, and the oxygenof ambient air. Vibration treatment ends once clinical signs ofreperfusion are identified or until emergency invasive treatment (i.e.PCI and/or emergency revascularization surgery) is established.

The preferred vibration apparatus for deliverance of vibration therapyis represented diagrammatically in FIG. 6, where an operator (not shown)provides input to processor 34 via interface 50 of the preferredvibrator 10. Interface 50 comprises a set of manually operated controlswitches (not shown), advantageously located for easy access on theexterior surface of housing 14 of vibrator 10. Processor 34 in turncontrols vibrator 10, delivering the prescribed frequency, displacementamplitude and displacement wave form (described later) of continuouslyapplied vibration to the target site (or sites) on the patient 20 via asole attachment interface. As an option to interface 50, other variantinterfacing means such as an electronic touch pad or key board (eitherlocated remote or on housing 14) may alternatively be employed.Processor 34 is advantageously located within housing 14 of vibrator 10,and comprises a programmable logic control of known type. The preferredvibrator 10 is particularly appropriate for first line treatment such asin emergency rooms and ambulances during transport, where in both casesnon-experts are operating the device. The preferred embodiment isdesigned to provide a simple and reliable first line response to AMIincidents, which can be operated with minimal training and easilyapplied in the field or emergency room setting.

Referring now to FIG. 7, in some cases it may be preferable to applyvibration therapy with an “advanced method” comprising use ofphysiological and mechanical monitoring or sensing equipment and varyingtiming and/or frequency algorithms for vibration delivery. With varyingalgorithms, cardiac phase dependent time and optionally frequency variedvibration therapy may be employed when best suited to the clinicalsituation. Enablement of the “advanced method” is provided via a variantcardiac phase controlled vibrator 11 (i.e. “variant 1”), which isadvantageously of like construction to preferred vibrator 10, but isadapted to receive and respond to more advanced commands from variantprocessor 35 and a variant interface 51. In this variation, both variantprocessor 35 and variant interface 51 are located remote from thehousing of variant cardiac phase controlled vibrator 11.

The needs for varying timing and frequency algorithms in vibrationtherapy will differ depending on the clinical presentation. For example,in cases of hemodynamically stable acute ST elevation myocardialinfarction; continuous vibration which is cardiac phase controlledwhereby approximately 50 Hz vibration is imparted during ventriculardiastole and approximately 100 Hz during ventricular systole may beemployed, which is suspected by the applicant of the present inventionto produce a more therapeutic result. Any known phase monitoring means(see below) may be used to determine the timing of the cardiac phase,and this is firstly determined automatically via variant processor 35,and then is optionally further fine-tuned by an operator via anadjustment (or “vibratory timing adjustment control”) made to variantinterface 51. Cases of complicating cardiogenic shock or unmanageablecongestive heart failure with acute ST elevation myocardial infarctiondictate diastolic only timed vibration. Vibration timed specifically tothe diastolic phase of the cardiac cycle provides a form of ventricularassist with a positive inotropic effect, and, as the diastolicmyocardium is particularly stiff in times of profound ischemia, thevibration signal exhibits excellent intra ventricular transmissibility(i.e. transversely propagated internal vibration) to ensure an agitativetreatment response to all areas of the coronary circulation. It issignificant that the conventional treatment of acute M1 with thecomplication of cardiogenic shock with thrombolytics only (i.e. with noadjunctive interventional or mechanical treatment) is extremelyineffective, with a low likelihood of reperfusion and a 63% in-housemortality reported.

In the advanced method, additional physiological monitoring equipment isprovided to make possible the application of special vibration timingalgorithms according to cardiac phase. Such physiological monitorsinclude; electrocardiogram (“ECG”) 36, impedance plethysmograph 40(optional), phonocardiography system 42 (optional), and noninvasiveblood pressure apparatus 44 (optional). The monitoring and sensingequipment, all of commercially known types, are interfaced with thepatient 20. A transesophageal accelerometer 38 placed on atransesophageal lead may be used, (as disclosed in Japanese Pat. No. JP4156823 to Takishima et al., incorporated herein by reference), toconfirm and monitor maximal sonic penetration to the esophagus, whichrepresents the posterior aspect of the heart. An external accelerometer39 is also provided, which is advantageously placed on shaft 17 ofvariant cardiac phase controlled vibrator 11 (“variant 1”), to assist inmonitoring the timing of vibration therapy in real time, and to confirmthe functioning (i.e. frequency and amplitude) of the applied vibration.Alternatively, variant processor 35 may optionally emit a signalindicating when variant cardiac phase controlled vibrator 11 (“variant1”) is active. The monitored physiological and mechanical outputinterfaces with variant processor 35, which is thereafter processed andsent to display monitor 52 for real time wave form display. Theoperator, based on the output displayed on display monitor 52, mayselect and modulate programmed timing and frequency algorithms designedto optimize therapy by entering a selection to variant interface 51which interfaces with the operator and sends commands to variantprocessor 35. For example (as mentioned previously), specifically timedsinusoidal cardiac phase controlled vibration at 50 Hz In ventriculardiastole and 100 Hz in ventricular systole, at maximum tolerable forceor displacement amplitude, is preferred for use with the advanced methodin the treatment of hemodynamically stable ST elevation infarcts.Vibration timed exclusively to the diastolic phase of the cardiac cycleat 50 Hz (known to produce a positive inotropic effect), is preferredfor hemodynamically unstable ST elevation infarcts, (e.g. withassociated cardiogenic shock). ECG 36 output is essential to provide atiming differentiation means between the diastolic and systolic phase ofthe cardiac cycle. Variant processor 35 will interpret the ORSdeflection as the onset of systole, and will assign a preprogrammeddefault rate related time delay to dictate the timing of the onset ofdiastole. The default time delay may be monitored and adjusted by theoperator (i.e. with the vibratory timing adjustment control), based onphysiological signals viewed upon display monitor 52. Monitoring ECG 36output can additionally provide information to heart rhythm andreperfusion which is represented by a sudden decrease in ST segmentelevation.

Display monitor 52 comprises a CRT (or other) monitoring screen enablingreal time output wave form display, and digital read outs plusannotations where all necessary information for an operator to makejudgments is displayed. Variant interface 51, comprises a combination ofan electronic control touch screen and a keyboard entry (although otherknown interfaces such as voice recognition, push buttons, slidingswitches, control knobs or any other suitable interface may be used), toallow for selection and modification of: vibration displacementamplitude, displacement amplitude according to cardiac phase,displacement wave form selection, ECG 36 monitoring selection, low passECG filter (on/off), mode selection (i.e. diastolic vs. continuousvibration emission), vibratory timing adjustment control, and frequencyalgorithms. Variant processor 35 is adapted to receive and process inputfrom variant interface 51, and through analysis of the physiologicalinformation delivered from the monitoring equipment, control variantcardiac phase controlled vibrator 11 (“variant 1”) to cause vibration atthe time period, frequency, displacement amplitude and wave form, asselected by the operator. ECG 36 employs a standard monitoring system torepresent inferior (II, III, avF), anterior (V lead) and lateral (V5, I,aVL) electrocardiographic information, but may be of otherconfigurations. Impedance plethysmograph 40 comprises a commerciallyknown impedance plethysmography system enabling a relative comparison ofreal time changes in intra thoracic blood pressure. Impedanceplethysmograph 40 further relays the timing of the dichrotic notch(signifying the onset of diastole) to display monitor 52 and thereby tothe operator, making manual adjustments to the timing of the onset ofdiastolic vibration more accurate (however in the absence of impedanceplethysmograph 40, the onset of diastole may be judged at thetermination of the T wave of the wave form displayed from the ECG 36).The termination of diastolic vibration is triggered automatically byvariant processor 35 in recognition of the deflection of the QRS complexprovided by ECG 36 monitoring means. It is therefore important toachieve a good “tall” QRS complex on the chosen ECG 36 monitoring leadwithout a great deal of muscle artifact. A low pass ECG 36 filter(filter not shown), operational with a 40 Hz cutoff is included tominimize such artifact. A wedge filter (automatically set to thefrequency of the vibratory signal) is also included, to substantiallyeliminate vibratory artifact on the ECG 36 waveform trace.Phonocardiography system 42 of known type is optionally included as italso provides information as to the timing of the onset of diastole(i.e. by the initial deflection of the “S2” heart sound), and therebyprovides additional information to assist in the manual adjustment fordiastolic only vibration.

Noninvasive blood pressure apparatus 44 comprises a noninvasive realtime blood pressure monitor provided by arterial tonometry whichnon-invasively senses the pressure of the radial artery by way of anexternal pressure transducer to provide a real time arterial bloodpressure wave form, but may alternatively be a noninvasive bloodpressure monitor of any commercially known type, which quantifies theblood pressure of the patient 20. For example an automatic noninvasiveblood pressure cuff system could be utilized with periodic digitalreadouts sent to variant processor 35 and thereby to display monitor 52.An electronic strain gauge force meter (not shown) is optionallyemployed to monitor the engagement force of the variant cardiac phasecontrolled vibrator 11 (“variant 1”) to the chest wall (or thorax) ofthe patient 20. Alternatively, any commercially known gauge such as aweight scale may be used to determine the engagement force.Accelerometer 39, placed on the shaft 17 of variant cardiac phasecontrolled vibrator 11 (“variant 1”) is utilized to confirm thatappropriate vibration is being applied, and to provide a real timecomparison of treatment vibration application versus ECG 36 andoptionally impedance plethysmograph 40, and/or phonocardiography system42 wave form trace.

Regardless of method employed (i.e. “simple” or “advanced”), the patient20 should preferably be monitored by at least one clinician or nurseduring the course of vibration therapy for treatment of acute STelevation myocardial infarction. Pain and nausea may require anadjustment in the amplitude or engagement force of vibration or even acessation of treatment. The operator can readily adjust or remove thevibrator 10 (or provided variant) as required. Particularly using the“advanced method”, the operator or clinician may adjust the treatment tosuit patient 20 physiological status which is displayed on displaymonitor 52. For instance a sudden drop in blood pressure, usuallyindicating deterioration into cardiogenic shock, would be registered byplethysmograph 40 and/or noninvasive blood pressure apparatus 44. Theoperator may decide to discontinue continuous vibration therapy (i.e.vibration applied throughout the cardiac cycle), which may have anegative inotropic effect on heart failure, and switch to diastolic onlyvibration, which is known to provide a positive inotropic effect. Ifhemodynamic compromise is borderline, the operator may optionally limitor reduce the displacement amplitude of vibration selectively during thetime period of ventricular systole, while maintaining maximizeddisplacement amplitude during ventricular diastole.

In reference to FIG. 8, low frequency vibration via a plurality ofdisplacement wave forms with “displacement” on the vertical axis and“time” on the horizontal axis, (with respect to the movement of acontact 12) is shown. While the preferred embodiment incorporates use ofa sinusoidal vibration displacement wave form <a>, other displacementwave forms of vibration may alternatively be selected such as; squarewaves <b> (or “pulsed” or “percussive” waves, with a steep displacementrise), saw tooth waves <c> (with a gradual displacement rise),exponential waves <d> (with an acceletory, non-linear displacement rise)or any other linear or nonlinear wave shape (or combinations thereof)according to the invention. High impact square wave <b> vibration may beparticularly advantageous in some instances due to its known superiorpenetration and disruptive characteristics through human tissue.

The above methods of low frequency vibration therapy may be used forseveral pathologies and in different settings. Six prophetic examples ofclinical use illustrated in reference to the heart, in variousin-hospital or pre-hospital settings are as follows:

First, vibration therapy may be employed in an emergency room orambulance in the first line treatment of acute ST elevation myocardialinfarction, preferably adjunctive to thrombolytics, or any other form ofmedical therapy.

Second, also in an emergency room or ambulance as a first linetreatment, vibration therapy may be employed to reduce the dosage ofthrombolytics and/or anti-platelet agents required for those patientswhere thrombolytic therapy and/or anti-platelet therapy is relativelycontraindicated due to increased bleeding risks (and also to savecosts), or even eliminate the use of drug therapy entirely.

Third, vibration therapy may be employed in the in-hospital orpre-hospital setting for treatment of chest pain refractory to medicalmanagement in cases of Non-ST elevation M1 or cardiac ischemiapreferably as an adjunct to drugs such as but not restricted to IV or SLnitroglycerin, GP 2b-3a platelet inhibitors, and heparin. Lytics are notindicated in such cases. Gently applied vibration timed to the diastolicphase of the cardiac cycle (i.e. via the “advanced method”), which isknown to increase coronary flow in stable, ischemic, non occlusivestates (as per the teachings of JP 8089549 to Koiwa et al., incorporatedherein by reference), may be tried in these cases as a first measure tolimit vibration therapy and thereby limit potential bruising to thepatent 20 who may be anti coagulated. The intensity level of the appliedvibration may be gradually (or incrementally) increased to a thresholdof patient comfort. If diastolic only vibration does not relieve thechest pain (or if not available) continuously applied vibration (i.e.throughout the cardiac cycle, in systole and diastole) should beselected, which is more effective for more serious coronary syndromeswherein the mechanisms are either or both of coronary artery spasm andcoronary thromboses formation. Continuous vibration should preferably beapplied at incrementally increasing displacement amplitudes (or force)until the maximal levels of comfort and safety are realized and thesymptoms are relieved. This gentle method of progression of phasemodulation and displacement amplitude in ischemic but substantiallynon-infarcting syndromes is important as the situation is not acute, andthe patient will likely be (as previously stated) anti-coagulated andwill bruise easily.

Fourth, vibration therapy may be employed prophylactically in the stepdown telemetry unit or CCU for example, adjunctive to nitrates (and/orblood thinning medications) for more pronounced coronary events (i.e.with ST/T wave changes on the ECG telemetry monitor) which are otherwiserefractory to conventional drug management, whereby an acute denovoblood clot and/or acute coronary vessel spasm at the earliest of stagesmay be in the process of formation. Newly formed (or forming) bloodclots are easily disrupted and mobilized prior to the deposition offibrin by the vibration methods disclosed.

Fifth, vibration therapy may be applied to the chest wall in the cardiaccathlab setting as an adjunct to drugs such as nitroglycerine, nipride,verapamil, GP 2b 3a platelet inhibitors, and thrombolytics, for acute tosub-acute procedures prior to, during, or after PCI (or heartcatheterization), where there may be significant clotting in the arteryat the onset of or immediately following the procedure. Vibrationtherapy could for example be utilized pre-procedure, as an adjunct to GP2b 3a platelet inhibitors+− thrombolytics while the patient 20 is enroute to the cathlab for emergency PCI. Post procedure, vibrationtherapy may for example be appropriate in “no-reflow” or “slow-flow”situations following or during an intervention, for instance when clotsand/or micro emboli dislodge and affix themselves to the distal,arteriolar circulation to cause very poor flow, chest pain and injury.It should be noted that if chest wall vibration therapy where to beimparted during a heart catheterization (or PCI procedure), the guide ordiagnostic catheter should be withdrawn from the ostia of the selectedcoronary artery prior to initiation of the vibration therapy in order toavoid shear forces and possible dissection to the ostia of the coronary.

Sixth, vibration therapy may be employed in the community for acutestates of coronary insufficiency resulting in symptoms of possible acutemyocardial infarction refractory to nitroglycerine treatment in thepatient 20. Every bout of “angina” that patient 20 in the communityexperiences might represent an acute coronary event wherein a plaque hasruptured and a blood clot (and/or vessel spasm) has formed. In thesecases, patient 20 will typically have tried nitro spray*3, each dosespread five minutes apart, without relief of chest pain which may bequite severe. Patient 20 will then proceed to dial “911” for emergencyassistance, wherein the diagnosis of an acute coronary obstructionleading to an acute MI cannot be ruled out until professional carearrives. As stated above, hyper acute early clot formation isparticularly amenable to dissolution via mechanical agitation. Highamplitude vibration therapy concentrated to the chest wall in theseinstances can provide such agitation, and can be therefore(prospectively) an extremely important first line emergency tool, forcapturing the window of susceptibility of a newly formed blood clot anderadicate it before it has a chance to grow and harden, and cause damageto the myocardium, or even sudden death to the patient 20. Fortreatment, the patient 20 should be ideally resting in either the supineposition or seated comfortably upright in a chair. Ideally a friend orbystander should provide vibration therapy to the patient 20 (preferablywith the continued administration of nitrates) until symptoms havedissipated or until professional care arrives.

Vibration therapy is effective in emergency situations where an acutevascular obstruction has occurred and cell death or hemodynamiccompromise is imminent, particularly when there is a poor prognosis fordrug therapy alone and emergency invasive intervention is delayed or notavailable.

Acute pulmonary emboli and in particular saddle emboli (which involves acritical life and death situation) are also good candidates forexternal, transcutaneous vibration therapy adjunctive to standard drugtherapy (e.g. IV thrombolytics, anticoagulants etc.). Chest wallvibration to the vascular region of the lung (pulmonary vasculature) andpulmonary artery are readily achieved by the methods disclosed below.The underperfused body region in this case is the organ and tissues ofthe lung and, in the case of saddle emboli, the entire body. A frequencyof less than 1000+Hz, and preferably selected from the 1-120 Hz range atmaximum tolerable force or displacement amplitude is suitable for suchapplications. The choice of 50 Hz sinusoidal vibration is preferred, as50 Hz sinusoidal vibration can be delivered at relatively highamplitude, has excellent chest wall to thoracic cavity penetrability,and is also a well established frequency known to produce cavitation andacoustic streaming (to assist in thrombolytic to clot filtration), aswell as vascular dilation and clot disruption. As an option, square wave<b> (i.e. with a steep displacement rise for better penetration anddisruptive action), saw tooth wave <c>, exponential wave <d>, or anylinear or nonlinear (or combination thereof) displacement wave form, maybe used (see FIG. 8). As the lungs also reside in the thoracic cavity,the present invention also functions to vibrate the vasculature of thelungs and pulmonary artery with low frequency vibration. Ultrasonicimaging means to target the pulmonary artery (i.e. where saddle embolusis presumed the culprit) may be employed to target the vibrationtherapy. Without ultrasonic imaging, the preferred vibrator 10 (withpreferably a pair of contacts 12) is preferably placed to bridge thesternum at the level of the third intercostal space of the patient 20(which approximates the bifurcation point of the left and rightpulmonary artery). Alternatively, chest wall attachment may comprise aplurality of contacts 12 either bridging the sternum or applied to theleft sternal margin of preferably the third, fourth and fifthintercostal space. A frequency of less than 1000 Hz, preferably 1-120 Hzand optimally about 50 Hz is then applied at maximum tolerable amplitudein conjunction with a systemically delivered drug such as athrombolytic, anti-platelet, anticoagulant or vasodilatory drug. Theapplication of high amplitude low frequency vibration commencesadjunctively to drug therapy until signs of reperfusion or untilinvasive corrective measures may be established. Optionally, vibrationtherapy may be utilized independently (i.e. without a drug), or with adecreased dosage of drugs.

Vibration therapy may also be employed to treat acute CerebralVasculature Accidents, preferably once determined as ischemic or embolicin origin, adjunctive to thrombolytic therapy where brain function isstill arguably salvageable. Transcutaneous cranial vibration to thevascular regions of the brain of the patient 20 are readily achieved bythe methods below. The underperfused body region in this case is theorgan and tissues of the brain of the patient 20. The vibrator 10 (withpreferably a pair of contacts 12) is advantageously attached to theposterior aspect of the neck of the patient 20, however the lateral orposterolateral aspects of the neck may also be used. Alternatively,vibration may be applied directly to the cranium of the patient 20 via ahelmet (not shown), cushioned to avoid bruising to the head of patient20, which comprises an alternative attachment interface to vibrator 10.A frequency of less than 1000 Hz, and preferably selected from the 1-120Hz range, is then applied at a selected displacement amplitude (i.e.from 1 mm to 15 mm displacements), in conjunction with a systemicallydelivered drug such as a thrombolytic, anti-platelet, anticoagulant, orvasodilatory drug. The choice of 50 Hz sinusoidal vibration ispreferred, as 50 Hz sinusoidal vibration can be delivered at arelatively high displacement amplitude, and is a well establishedfrequency known to produce cavitation and acoustic streaming (to assistin thrombolytic to clot filtration), as well as vascular dilation andclot disruption. As an option, square wave <b>, saw tooth wave <C>,exponential wave <d>, or any linear or nonlinear displacement wave form(or combinations thereof) may be used (see FIG. 8). The displacementamplitude of vibration should be selected judiciously with the moreserious natured acute ischemic strokes (i.e. where there is a traumaticdeficit noted), preferably receiving relatively higher displacementamplitudes in keeping with an increased benefit to risk ratio (i.e.benefit of improved thrombolysis to restore vital function vs. risk ofcerebral bleeding). Optionally, vibration therapy may be utilizedindependently (i.e. without a drug), or with a decreased dosage ofdrugs.

Vibration therapy in accordance with the present invention may befurther utilized to facilitate the restoration of blood flow In acute,emergent peripheral arterial obstructions such as those occurring in thelimbs of a patient. When the obstruction (which is usuallythrombo-embolic in nature or involving acute thrombosis on a preexistingulcerative plaque) involves a critical segment of the arterial systemwhere the collateral potential of blood perfusion is poor, the clinicalpicture is dramatic with loss of limb viability and amputation imminentif not treated effectively within six hours. Transcutaneous peripheralvibration to the vascular region of the effected peripheral body part(including all organs and tissues distal to and including the claviclesand groin region of the patient 20) are readily achieved by the methodsdisclosed below. A vibration frequency of less than 1000 Hz, preferably1-120 Hz, and optimally 50 Hz sinusoidal vibration, is appliedtranscutaneously to the presumed culprit area, at a high force ordisplacement amplitude (preferably at the highest levels deemedtolerable and safe to the patient 20). As an option, square wave <b>,saw tooth wave <C>, exponential wave <d>, or any linear or nonlinear (orcombination thereof) displacement wave form, may be used (see FIG. 8).Vibration therapy is preferably used in conjunction withpharmacologically active agents such as thrombolytics, anti-platelets,vaso-dilatory or anticoagulant drugs as a first line method to restoreearly flow, and to also act as a bridge to emergency corrective surgeryor intervention. A singular or plurality of contacts 12 are utilized toprovide maximal agitative vibration energy imparted to the culprit area.The contacts 12 are placed on the limb surface affected, with contactpreferably established at the point at which distal pulses are lost.Typical attachment areas comprise the pelvis/groin area (i.e. iliac andfemoral arteries), thigh (femoral artery), popliteal space (poplitealartery), lower leg (tibial artery), periosteum of the clavicle and firstrib (sub-clavian artery), soft tissue area between the clavicle andtrapezius muscle (sub-clavian artery), axilla (axillary artery),brachium (brachial artery), anti-cubital fossa (brachial artery), andforearm (radial artery). The contacts 12 are advantageously comprised ofsilicone rubber, however any commercially available material, preferablyresilient and substantially non-distortable may be used to form thecontact surface of contacts 12. Alternatively, the contact surface ofspecially adapted “peripheral” contact heads (not shown) are malleableto enable a more exacting vibration contact to complex, uneven and rigidcontours (such as in contours overlying or directly adjacent to bone) ofthe body surface of the patient 20. The peripheral contact heads in thisvariation (which are of a known type) are comprised of a solid basepiece, which partially encapsulates an incompressible fluid with asemi-compliant membrane overlying the active end of the base piece andincompressible fluid. For acute peripheral vascular obstructionapplications, the engagement means of vibrator 10 may be by hand, byclamp 100, or alternatively via a belt engagement system with Velcro™strap securement (described later). Ultrasonic imaging means to target aculprit blood clot within a culprit vascular region may be employed toenable direct visualization and targeting of the vibration therapy withhighest efficiency. The application of vibration optionally commenceswith adjunctive drug therapy until signs of reperfusion or untilinvasive corrective measures may be established. Optionally, vibrationtherapy may be utilized independently (i.e. without a drug), or with adecreased dosage of drugs.

Referring again to FIG. 1, the preferred embodiment of the vibrator 10(i.e. in the emergency treatment of ST elevation M1) is applied by thehands of an operator with the patient 20 lying substantially in thesupine position.

The preferred vibrator 10 of the present invention is operable togenerate and emit vibration selectably in the 1-120 Hz range. A secondvariant “research” vibrator (i.e. “variant 2”—not shown), is alsoprovided, being adapted to operate in a higher frequency range, above150 Hz, and up to 1000 Hz (which is designed primarily for researchapplications and applications directed by ultrasonic imaging). Thus,vibration therapy within the range of 1-1000 Hz is provided according tothe invention.

Vibrator 10 contains a high powered linear stepper motor (notshown-located within housing 14), with sufficient power to enableoperation at engagement forces of up to approximately 100 N. Vibrator 10is characterized to enable selective frequency and displacementamplitude control in the 1-120 Hz and 1-15 mm range respectively, aswell as selectable displacement “wave form” control (comprising aselection of sinusoidal <a>, square <b>, saw tooth <c>, and exponential<d> wave shapes-see FIG. 8). Vibrator 10 is further programmable to emitany other linear or nonlinear displacement wave shape (or combinationthereof). Use of vibrator 10 enables the delivery of high amplitudeforces of vibration concentrated to the selected body surface treated.

The active end of the provided linear stepper motor is operativelylinked with and drives the proximal “non-active end” of shaft 16 (notshown-within housing 14), which is thereafter projected through housing14 (now shown), to enable contact with the selected attachmentinterface. As an option, a displacement amplifier (such as a lever or apneumatic displacement amplification system) may be incorporated toestablish the necessary displacement amplitude emission required.

The selection of displacement amplitudes ranging from 0 (off), 1 to 15mm deflection is provided by an amplitude regulatory mechanism which isincrementally controlled by the operator. The amplitude regulatorymechanism is enabled by the provided linear stepper motor stroke lengthcontrol. The stroke length control is coordinated via commands fromprocessor 34 and interface 50, which all taken together comprise the“amplitude regulatory mechanism” of vibrator 10. Vibrator 10 is alsooptionally programmable to enable selectable vibration force (or power)control at a given frequency, as an alternate to (or in addition to) theprovided selectable displacement amplitude (or stroke length) control.

Operation of the preferred vibrator 10 is as follows. The operatorinputs commands to the interface 50, which thereafter sends commands toprocessor 34, located upon and within (respectively) housing 14 of thevibrator 10. Commands from interface 50 to processor 34 indicate theoperator selection of various vibration signal parameters such asemission frequency (i.e. 0 off, 1-120 Hz), vibratory displacementwaveform emission shape (i.e. sinusoidal <a>, square <b>, saw tooth <c>,or exponential <d>—see FIG. 8), and stroke length (i.e. 0 off, 1-15 mmdeflection). Processor 34 (with signal generator and amplifier)generates the appropriate signal at the appropriate power level to feedthe input of the provided linear stepper motor.

As an option, vibrator 10 will also contain programming and controls toenable the selection of variable frequency response algorithms (orvariations in vibration cadence), such as in the Sharper Image MassagerModel HF 757 incorporated herein by reference.

A fan (not shown) is advantageously disposed within housing 14 ofvibrator 10, (as well as a pair of ventilation holes through housing14—also not shown), to assist convective air cooling of the providedlinear stepper motor therein, which enables prolonged application timessuch that the device will not overheat. Alternatively, any other knownsuitable cooling mechanism may be used. Vibrator 10 is also optionallyequipped with a controllable heating system for heating the contactsurface of contacts 12, which may add benefit to clot disruption insuperficial treatments of thromboses. Any one of the amplifier or signalgenerator within processor 34 or interface 50 (in any combination) mayoptionally be disposed remote from housing 14 of vibrator 10, such as toenable a more compact and lighter weight hand held instrument.

Vibrator 10 is powered by an AC power cord, or as a second means via aportable DC battery pack (not shown), which is slide-ably and removablydisposed within the handle of housing 14. The DC battery pack isadvantageous as it enables operation of vibrator 10 in the field whereinno AC power is commonly available.

It should be emphasized that vibrator 10 as herein described comprises a“preferred” means (or apparatus) for the deliverance of emergencyvibration therapy in the treatment of acute vascular obstructions, andaccordingly may be varied in many ways to enable function of aneffective emergency response system. In essence, any low frequencynon-invasive vibrator (or percussion, or oscillation device by othername) with an attachment interface suitable to enable direct selectedbody surface contact, operational in the range of 1-120 Hz (andoptimally within the range of 20-120 Hz), with a displacement amplitudeenablement of greater than 2 mm (and preferably greater than 4 mm),which is operable under engagement forces at least 5-10 N (andpreferably greater than 20 N), may be used to provide an effectiveemergency tool in the emergency response system. Possible variations tovibrator 10 for enablement of the emergency system are described later.

The variant research vibrator (“variant 2”) of the present inventioncontains a high powered voice coil adapted to generate vibration athigher frequencies within the 1-1000 Hz range. The variant researchvibrator (“variant 2”), is characterized to enable both selectivefrequency and force (or power) control at a given frequency, and is alsooperational under engagement forces to the human body of up to about 100N. Frequency settings above 150 Hz have limited displacement amplitudeemission capability, in keeping with clinical safety concerns and themechanical constraints of the provided system, and are thereby confinedto the low millimeter to sub millimeter emission ranges (i.e. as low asabout 0.1 mm). The provided high powered voice coil (which is locatedwithin a housing adapted in size and shape for hand held use) isoperatively linked to the proximal “non-active end” of the vibratoryshaft of the variant research vibrator (“variant 2”). The vibratoryshaft is thereafter projected through the housing, enabling removableattachment to any of the attachment interfaces described according tothe invention. The variant research vibrator is also powered in likefashion to the preferred vibrator 10 (as described above); through ACpower cord and removable DC battery pack. The variant research vibratoris of preferred use in conjunction with simultaneous ultrasonic imaging(as per the dual function system-described earlier), as the lowdisplacement amplitude signal at higher frequencies requires directionand the establishment of a sonic penetration window, to ensuretherapeutic penetration to target vascular areas within the patient 20.

It should be understood that the choice of a voice coil is not criticalto enable vibration therapy in the 1-1000 Hz range, and a high poweredperistaltic linear motor for example with frequency and power (orforce/stroke) control, may alternatively be employed. An exemplaryperistaltic linear motor may be comprised of a magnetostrictive materialoptimally incorporating Terfenol D. Alternatively, a linear steppermotor assembly could be used independently, or in conjunction with themagnetostrictive material.

A variant “light weight” vibrator (i.e. “variant 3”—not shown) is alsoprovided according to the invention (described later), which enablesmaximum displacement amplitude emissions limited to 10 mm deflectionswith sufficient power to enable operation under engagement forces to thebody surface of the patient 20 of up to about 50 N. Variant light weightvibrator 10 (“variant 3”) is of like design to vibrator 10, but is oflighter weight (i.e. with a smaller, less powerful linear stepper motor)and is thereby better suited for self administration by the patient 20,who may be too weak to hold a heavier device.

Yet another variant “heavy duty” vibrator (i.e. “variant 4”—not shown)of like design to vibrator 10 but of greater weight and of higher power(i.e. with a larger, more powerful linear stepper motor) is provided forobese patients (or when the backside of the patient 20 is utilized) andwill not dampen its oscillations when engagement forces of significantlygreater than 100 N are applied.

The preferred vibrator 10 is of a size and weight well suited for clamp100 engagement, belt engagement (described later) or engagement by thehand of an operator preferably via a double-handed technique. Thevariant lightweight vibrator (“variant 3”) is of a size and weight wellsuited to single hand or double handed engagement. The variant heavyduty vibrator (“variant 4”) is of a size and weight more suited to clamp100 engagement, or engagement by both hands of an operator. The variantheavy duty vibrator (“variant 4”) is well suited for use with obesepatients, or in cases where the backside of the patient 20 is utilized(described earlier), wherein higher displacement amplitudes andengagement forces may be required to ensure therapeutic penetration.

The housing 14 of vibrator 10 (and all provided variants) isadvantageously made of ABS Cycolac™ material, however any alternativedurable and lightweight material (such as polycarbonate or stainlesssteel) may be used.

The preferred vibrator 10 (and provided variants) is powered by batteryor power cord at a range of voltages (e.g. North America-110, 120 V,Europe-220V, Japan 95, 105 V, Australia 240 V) and is (as stated)operable both by battery and power cord for emergency settings. Thevibrator 10 (plus all provided variants), cumulatively enables aselection means for a range of frequencies in increments of 0 (off), 1,5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 150, 200, 300,400, 500, 600, 700, 800, 900 and 1000 Hz (although other variations infrequency selection may be employed).

Detachable contacts 12 are provided in a plurality of sizes, (i.e.small, medium and large), and made substantially of silicone rubber,however any resilient yet non-obtrusive material (preferably shaped witha convex contact surface), to allow comfortable application against thebody of patient 20 may be used. The contacts 12 are sized to makecontact with an intercostal space of the human body, and rest evenlyagainst the upper and lower rib, with an outward dome shaped convexityto ensure soft tissue contact and concentrate vibration therapyeffectively. The preferred contact 12 advantageously comprises a semispherical dome shape, with a flat planar circular base (the base beingof similar size to the head of a stethoscope), wherein the base rangesin size between 2 cm, 3 cm and 4 cm diameter. It should be understoodthat the exact shape of contacts 12 (i.e. a semi spherical dome) is notcritical, and that any convexly shaped contact head may be used, as longas efficient seating within the intercostal spaces of the patient 20 isenabled. Optionally, a variety of contacts comprising suction cups (notshown) are provided to enable an additional active retraction force,provided the patient 20 is not significantly diaphoretic. A soft rubberlining (or more specifically, a vinyl lining with foam rubber underlayof known type) may optionally overly the engagement surface of contacts12 in order to impart a more comfortable application (which isespecially useful for extremely tender skinned females with fleshybreast tissue who often are very sensitive to pressure applications tothe chest wall). It should also be understood that the exact size ofcontacts 12 is not critical, and a selection of variant contacts (notshown) with even smaller contact surfaces may be used, enabling a directseating within the rib space of the patient 20 such that the ribsthemselves are minimally or not touched. This manner of chest wallcontact provides a more comfortable application for some individuals.

The preferred embodiment comprises a pair of adjustably spaced contacts12, separated by bifurcated connector 13 which is attached to shaft 16of vibrator 10, to provide concentrated therapy (preferably) to eitherside of sternum at the selected intercostal space as per the prescribedmethodology. Alternatively, to avoid unnecessary bruising (or trauma) tothe chest wall, a solitary contact 12 (either attached directly to shaft16 or via the variant connector-described earlier) placed leftward thesternum can be utilized, this method particularly suitable in cases ofknown Anterior or Lateral AMI (i.e. wherein leftward coronaryinvolvement is diagnosed). In a further variation, to optimize sonicpenetrability to the heart and to account for variable location of theheart within the thoracic cavity, a plurality beyond a pair of contacts12 may be used. In this case, bifurcated connector 13 further utilizesthe incorporated support structure 24 (depicted in FIG. 4), to allow forthe addition of up to two slide-able and lockable sleeves 23, whereineach sleeve 23 incorporates a pair of support arms 22, with each supportarm disposing at least a single contact 12. Placement of the pluralitybeyond a pair of contacts 12 could be, for example along, or justlateral to the anatomic right and left sternal border, encompassing the3rd, 4th and 5th intercostal spaces. In yet another variation, variantconnector 19 disposing two pairs of adjustably spaced contacts 12, maybe applied to bridge the sternum along the 3rd and 4th intercostalspaces, along the 4th and 5th intercostal spaces, or even along the 3rdand 5th intercostal spaces of the patient 20.

To maximize sonic penetrability in particular to the left anteriordescending artery, the vibrator 10 and chosen attachment interface maybe placed more anatomically leftward with respect to the patient 20,such that one or more contacts 12 will interface with the left midclavicular line (or thereabouts). Alternatively, any one of the utilizedcontacts 12 may be slide-ably placed more laterally along any one of thechosen anatomically leftward oriented support arms 22 (i.e. relative topatient 20), with the position of vibrator 10 remaining substantiallyover the sternum of patient 20. In yet a further variation, stimulationof the left mid clavicular line of the patient 20 may be ensured via theuse of a second vibration device with second attachment interface,preferably running in phase with the vibrator 10 (or equivalent) toavoid destructive interference of the vibratory signal

Referring again to FIG. 7, peripheral devices to variant cardiac phasecontrolled vibrator 11 (“variant 1”) are required for use of the“advanced method” variation of the invention. The advanced method isspecifically designed for cardiac use, to enable cardiac phasecontrolled vibration therapy (timed in accordance to the cardiac cycle)and the optional use of frequency algorithms to optimize the system.

Display monitor 52 (located remote to the housing of variant cardiacphase controlled vibrator 11<“variant 1”>) receives output from variantinterface 51, and peripheral physiologic sensors (as specified below)via variant processor 35. Display monitor 52 displays: ECG 36 output (upto three leads, e.g. V lead (anterior), Lead II (inferior) and V5(lateral)); a digital readout of heart rate; external accelerometer 39wave form output comprising the delivered surface vibration displacementamplitude on the vertical axis in (mm), and a real time display movingright to left at 25 mm/second to match the waveform output of ECG 36 inreal time on the ‘horizontal’ axis; the waveform output of optionalimpedance plethysmograph 40 also moving in real time to match the outputof ECG 36 (to monitor relative real time blood pressure, and inspect fortiming of diastolic therapy); optional phonocardiography system 42signal trace; the chosen frequency and mode of delivery (writtenannotations); the chosen displacement amplitude of the therapy (writtenannotation); and optionally a noninvasive blood pressure wave formoutput also moving in real time to match ECG 36 wave form output vianoninvasive blood pressure apparatus 44 arterial tonometry, to supportan absolute value to the otherwise relative plethysmography wave formanalogue. As an alternative to arterial tonometry, a noninvasiveautomatic blood pressure cuff system may be used, wherein a periodicdigital readout of systemic blood pressure may be displayed on displaymonitor 52.

Variant interface 51 comprises a combination of an electronic controltouch screen and keyboard entry which is (as stated previously) alsolocated remote to variant cardiac phase controlled vibrator 11 (“variant1”), and is preferably placed alongside display monitor 52 and variantprocessor 35 on a portable work bench or stand (not shown). Variantinterface 51 enables the reception of input from the operator andsupplies the interface with variant processor 35. Variant interface 51is adapted to receive and transmit information relating to: the mode ofvibration to be delivered (i.e. continuous, or diastolic onlyvibration); the displacement amplitude of vibration (0 off, 1-15 mmdisplacements); the displacement amplitude of vibration according tocardiac phase (0 off, 1-15 mm displacements); the frequency of vibration(0 off, 1-120 Hz); the frequency according to cardiac phase; thedisplacement wave form type (i.e. sinusoidal, square, saw tooth orexponential); the fine tuning control of vibration emission timing (or“vibration emission timing control”); the preferred ECG 36 lead to beutilized for determining or “tracking” the QRS complex via variantprocessor 35; and an electrocardiographic low pass frequency filter(i.e. with 40 Hz cutoff) suitable for eliminating muscle tremor andvibrational artifact from the resultant ECG 36 trace prior to processingvia variant processor 35.

Variant processor 35 receives information from the physiologicalmonitoring and sensing equipment and variant interface 51, and providesoutput to display monitor 52 and variant cardiac phase controlledvibrator 11 (“variant 1”). A preprogrammed, default rate related timedelay tracking the deflection of the QRS complex (used to signify andelectronically trigger the onset of diastolic vibration) is provided byvariant processor 35 programmable control. Variant processor 35 therebyis enabled to determine systolic and diastolic phases based on ECG 36output. The beginning of the diastolic phase of vibration is furtheradjustable by the operator according to an additional operator input (orvibration emission timing control) to variant interface 51, based oninformation gained by physiological timing parameters as viewed ondisplay monitor 52. These timing parameters are represented by; the waveform produced by accelerometer 39 on shaft 17 (which defines the timingand amplitude of the applied vibration), the wave form produced by ECG36 (which defines the beginning of systole via the onset of the QRScomplex), and optionally impedance plethysmograph 40 (which defines thebeginning of diastole via the dichrotic notch of the arterial wave formanalogue). As a further option, phonocardiogram 42 is used to definewith more exacting precision the onset of diastole (i.e. via the initialsplit of the “S2” heart sound signifying closure of the Aortic Valve).Phonocardiogram 42 however is not useful in continuous mode vibrationtherapy because of the continuous vibration noise, which contaminatesthe signal. In the case where both impedance plethysmograph 40 andphonocardiography system 42 are not employed, the onset of diastole canbe approximated as (and/or verified by) the termination of the T wave asseen on the waveform output of ECG 36. Variant processor 35, uponreceiving input from variant interface 51, and upon receivinginformation from the physiological monitoring and sensing equipment,will process the information and provide output to variant cardiac phasecontrolled vibrator 11 (“variant 1”) which applies the selected timing,mode, displacement wave form, frequency and displacement amplitude ofvibration therapy.

ECG 36 comprises a six electrode system, with a left arm, left leg,right arm, right leg (ground) and an anterior pre-cordial lead (modifiedV lead preferably placed on the sternum) and a lateral pre-cordial lead(V5). Output from leads 11, modified V lead, and V5 are preferablydisplayed on display monitor 52. Any lead may be selected for variantprocessor 35 automatic tracking of the QRS complex, with the leadpresenting with the tallest QRS complexes and/or relatively smallest Twaves preferred to ensure appropriate tracking and avoid “doublecounting”. In an option, a pair of ECG electrodes may be advantageouslyincorporated within or mounted upon the contact surfaces of the contacts12, to enable an expedited means of obtaining electrocardiographicinformation.

Impedance plethysmograph 40 requires the placement of two electrodes onthe arms of the patient 20 and the application of a minimal current inorder to monitor relative changes of blood pressure in real time,checking, for example, for any beneficial inotropic effects withdiastolic only vibration in cardiogenic shock patients, or suddendeterioration of blood pressure during treatment in an otherwisehemodynamically stable case of evolving myocardial infarction. Thepresent invention employs a Tektronix™ type 3C66 impedanceplethysmograph system; however any known impedance plethysmographysystem may be used for plethysmograph 40. Impedance plethysmograph 40 isalso employed to check the timing of the closure of the aortic valve andtherefore the beginning of diastole, and is useful to confirm or tofacilitate the manual adjustment (or vibration emission timing control)of the default rate related time delay set after sensing of the QRScomplex to ensure that diastole is captured properly in the timingalgorithms. Alternatively, a variant photo plethysmograph (such as theTektronix™ Plethysmography Pulse Sensor) placed to the finger orforehead of the patient 20, with wave form signal output to displaymonitor 52 (to inspect for inotropic changes) may be employed. Impedanceplethysmograph 40 is preferable as it yields a closer analogue trace ofa central arterial wave form (i.e. yielding an closer approximation ofthe true timing of Aortic Valve closure via the dichrotic notch) thanthe variant photo plethysmograph which incorporates an analogue trace ofa peripheral arterial wave form.

Phonocardiogram 42 is of a commercially known type, consisting of asmall microphone placed on the chest wall which provides output todisplay monitor 52 representing the heart sounds in time with ECG 36,plethysmograph 40 and accelerometer 39 signals. The heart sound “S1”represents the onset of systole, and the initial component (or “split”)of the heart sound “S2” represents the onset of diastole.Phonocardiogram 42 can with extreme precision, provide the timing ofaortic valve closure marking the onset of diastole, however the deviceis limited to diastolic only mode vibration therapy as continuous modevibration contaminates the audio trace.

Noninvasive blood pressure apparatus 44 comprises a modem state of theart arterial tonometry noninvasive blood pressure monitoring system(i.e. Pilot arterial tonometry device manufactured by Colin MedicalInstruments Corp.). Optionally, a noninvasive blood pressure monitor,comprising a blood pressure cuff system which takes a periodic bloodpressure reading from the arm of the patient 20 and displays theinformation on display monitor 52, may be used. Vibration therapy, inthis latter example, may be programmed to temporarily cease during themeasurements of the blood pressure cuff system to avoid interference inthe audio blood pressure measurements.

External accelerometer 39 (i.e. Shin Nipon Sokki C. Ltd Emic 540) isplaced on shaft 17 of variant cardiac phase controlled vibrator 11(“variant 1”) to monitor the timing, frequency and displacementamplitude of emitted vibration from variant cardiac phase controlledvibrator 11 (“variant 1”). Optionally, transesophageal accelerometer 38(i.e. Shin Nipon Sokki Co. Ltd Emic 540M) placed on a transesophageallead is used to monitor chest wall penetration of low frequencyvibration to behind the heart. Alternatively, any commercially availableminiature accelerometers can be used for either application.

A strain gauge force transducer (not shown) or optionally a weight scaleto indicate the engagement force of contact or contacts 12 against thechest wall (or other body part) of the patient 20 is optionallyprovided.

It should be understood that the location of variant interface 51,display monitor 52 and variant processor 35 relative to variant cardiacphase controlled vibrator 11 (“variant 1”) is not critical to enable useof the advanced method, and is provided as separate distinctly locatedelements (e.g. on a portable workbench) only to facilitate operativelinks between the instruments and necessary sensing and monitoringequipment which may be quite extensive (especially in the case whereinall possible sensing and monitoring equipment are utilized). Forexample, in an alternative embodiment, variant cardiac phase controlledvibrator 11 may be altered to comprise a functionally self containedoperator held unit (or device), comprising a display means (such as aLED display on the housing of the device), a control means (such ascontrol switches on the handle of the device), a cardiac phasemonitoring means (such as an ECG monitor operable in conjunction with oras part of the device), a vibratory emission monitoring means (such asan accelerometer system placed on a vibratory component of the device oralternatively a vibration emission indicator), and a processing means(such as a microchip or other programmable logic controller locatedwithin the housing of the device). This “self contained” arrangement ofthe cardiac phase controlled vibration delivery system may beadvantageous to an operator (or paramedic) in the field, whereinmaneuverability and ease of portability of the utilized apparatus areimportant factors towards expediency and effectiveness in emergencysituations.

Referring now to FIG. 9, a perspective view of a variation of thepreferred embodiment, a hand held single imaging/treatment probe (hereinset forth as the “variant dual function imaging vibration device 15”),and method as applied to the patient 20 is shown. This system (as perthe “dual function system” described earlier) employs both low frequencyvibration and high frequency ultrasonographic imaging (HFUS) takentogether in concert (simultaneously) via a single combined hand heldtransmission unit, for visually directing low frequency vibrationtherapy within the body of the patient 20. The attachment interface ofvariant dual function imaging vibration device 15 contains an ultrasonicimaging transducer (not shown-located at the active end of variant dualfunction imaging vibration device 15, proximate patient 20), whereby animage can be viewed on ultrasonographic 2-D display 17. The ultrasonicimaging transducer is operatively connected (or acoustically coupled) toa low frequency vibration source (also not shown-located within thehousing of dual function imaging vibration device 15) such that uponactivation, when the low frequency vibration source generates vibration,the ultrasonic imaging transducer vibrates and thereby is enabled todeliver low frequency vibration simultaneously (i.e. together in realtime) with HFUS imaging, all via a shared contact surface to the patient20. An optional weight added within or exterior to the housing ofvariant dual function imaging vibration device 15 (weight not shown),adds inertia to the system to ergonomically assist the operator (i.e. toapply engagement force) during hand held placement of dual functionimaging vibration device 15. An example of a useful ultrasonic image 18(in this case an image of the heart is depicted), is shown onultrasonographic 2-D display 17.

The vibration source of the variant dual function imaging vibrationdevice 15 advantageously comprises the same active components ofpreferred vibrator 10 (described earlier), and thereby enablesselectable displacement amplitude and selectable displacement wave formcontrol within a 1-120 Hz range. It should be understood however thatthis particular selection of vibration source is not critical to enableuse of the dual function system, and any known vibration source operableto generate vibration within the 1-1000 Hz range (so long as thetherapeutic vibration wave form does not disable or interfere with thenecessary ultrasonic imaging wave form) may be used, regardless of thelevel of provided vibratory emission control. Such vibration sources mayfor example comprise but not be limited to; linear stepper motors,linear stepper motors with displacement amplification, linear(non-stepper) motors, rotary motors with a rotary to linear conversionelement such as a cam or crank, eccentrically spinning weights,magnetostrictive actuators, voice coils, shakers (e.g. with or withoutneodymium magnet transducers), and ceramic servo motors coupled toeither a rotary (with cam) or linear stage. The preferred vibrationsource should be operable at high force or displacement amplitudesettings while under load, such as to optimally enable a high energypenetrative system of vibration therapy (or oscillatory or percussivetherapy by other name).

In a variation to the above dual function system (i.e. apparatus), asimply adapted ultrasonographic imaging transducer is provided, which isreadily incorporated for use as an attachment interface via removableattachment to shaft 16 of vibrator 10. In reference to FIG. 10, thisvariation of the dual function system utilizes variant “ultrasonographicimaging” contact 60, advantageously comprising semi spherical siliconedome 61 attached to and partially encapsulating a distal active end of apediatric HFUS imaging transducer of known type. Rectangular slit 62 iscentered at the curved “distal”, contact surface of semi sphericalsilicone dome 61 to provide for a minimal protrusion of engagement face63 (or imaging contact surface by other name) of the pediatric HFUSimaging transducer. This arrangement enables stable contact of bothengagement face 63 (i.e. for imaging), and the distal contact surface ofsemi spherical silicone dome 61 (i.e. for improved seating andtransmission of low frequency vibration) to the chest wall, or otherbody part, of the patient 20. The “proximal” end (i.e. away from patient20) of variant ultrasonographic imaging contact 60 comprises housing 64for the electronic components of the provided pediatric HFUS imagingtransducer. Hollow connecting column 65 is attached to and projectedfrom housing 64, which enables removable attachment (by friction) toshaft 16 of vibrator 10 (or to the shaft of any of the providedvariations to vibrator 10 according to the invention), however any knownmeans of attachment (fixed or removable) may be used, as long as a soundvibratory connection is established. In this variation to the dualfunction system, shaft 16 once activated, vibrates connecting column 65,which vibrates housing 64 for the electronic components of the pediatricHFUS imaging transducer, which in turn vibrates attached semi sphericalsilicone dome 61 and engagement face 63, which taken together comprisesvariant ultrasonographic imaging contact 60. The electronic control cord(not shown) of the pediatric HFUS imaging transducer is optionallyremovably secured to the exterior surface of housing 14 of vibrator 10.The electronic control cord is thereafter removably attached to anultrasound imaging apparatus (not shown) of known type; however anycommercially available ultrasonic imaging apparatus may be adapted foruse.

It should be understood that while ultrasonographic imaging contact 60of the dual function system incorporates the use of a partiallyencapsulating structure (i.e. semispherical silicone dome 61) disposedabout the provided distal active end of the pediatric HFUS imagingtransducer to improve contact and transmission of the low frequencytherapeutic vibration, this arrangement is not critical, and thepediatric HFUS imaging transducer (or any other known ultrasonic imagingtransducer) may be optionally applied alone (or by any other means),directly to the skin surface of the patient 20, without such anaccompaniment. Furthermore, while a pediatric variety of HFUS imagingtransducer is preferred because of its smaller size (i.e. to enableoptimal rib space application), alternatively, any known ultrasonicimaging transducer adapted in size and shape to enable human contact(preferably of a size to enable seating within a rib space) may beadapted for use.

As a further option of enablement to the dual function system (and yetanother variation), an ultrasonic imaging probe (or preferably variantultrasonographic imaging contact 60 as described above) may be adaptedfor attachment to the anatomically leftward oriented (relative topatient 20) attachment site of bifurcated connector 13 of vibrator 10(or alternatively any equivalent bifurcated attachment interfacestemming from any low frequency vibration source operable to generatevibration in the 1-1000 Hz range). This arrangement enables ultrasonicimaging guided placement via the preferred pair of attachment sites(i.e. to the chest wall of the patient 20), wherein the ultrasonicimaging transducer (or variant ultrasonographic imaging contact 60) isplaced to an application site on the patient 20 comprising a determinedfeasible sonic penetration window (as per the methods describedearlier), which will usually be near the sternal margin, at theanatomically leftward third, fourth or fifth intercostal space. Theopposing (or anatomically rightward oriented contact, which may or maynot comprise an ultrasonic imaging transducer), is preferably placedanatomically rightward to the sternum at the same determined intercostallevel, or optionally one intercostal spacer lower (or inferior) as perthe methodology described earlier. It should be understood that theincorporation of one, or more than one ultrasonic imaging transducer maybe used, in any number of orientations according to the invention (i.e.depending on the style of attachment interface selected).

A “multifunction system” is also provided, which in addition toproviding a means of transmission for low frequency vibration therapyconcurrently and simultaneously with ultrasonic imaging via a singletransmission instrument (i.e. as above in the “dual function” system),further enables a LFUS treatment wave form emission. A variant“ultrasonographic imaging and LFUS treatment” contact (not shown)adapted for removable attachment to shaft 16 of vibrator 10 (andprovided variants), with low frequency ultrasonic treatment emissioncapabilities as well as high frequency ultrasonic imaging capabilities,is provided. The variant ultrasonographic imaging and LFUS treatmentcontact comprises an ultrasonic phased array imaging transducer mountedupon and acoustically coupled to the active surface of a low frequencyultrasonic transducer (both of known types), such as to enabletransmission of the LFUS treatment wave form emission through the activecomponents of the ultrasonic phased array imaging transducer, andthereby to the patient 20. The low frequency ultrasonic transducer (orULFUS transducer”) component of the multifunction system advantageouslycomprises a piezoelectric actuator which is operational to emit afrequency at 27 kHz, which is a frequency known for its superior tissuepenetration characteristics and thrombo-disruptive properties (althoughother LFUS frequencies within the range of 20-100 kHz may be used, viathe incorporation of alternate piezoelectric actuators). The LFUStransducer and ultrasonic phased array imaging transducer assembly worktogether simultaneously and nondestructively, to supply continuous highresolution imaging with HFUS and simultaneous treatment with a LFUS waveform, all in conjunction with low frequency (i.e. sonic to infrasonicrange) vibration therapy.

Variant ultrasonographic imaging and LFUS treatment contact, (as withvariant ultrasonographic imaging contact 60-described earlier), is alsoremovably attached to shaft 16 of vibrator 10 (or provided variant) byfriction via a hollow connector (not shown), wherein in this case, thehollow connector is attached to the “proximal” non-active end of theLFUS transducer electronic housing. Alternatively, any known attachmentmeans (removable or fixed) may be used, as long as a stable vibratoryconnection is established. A first electronic control cord joins thevariant ultrasonographic imaging and LFUS treatment contact to anultrasonic imaging device, and a second electronic control cord joinsthe variant ultrasonographic imaging and LFUS treatment contact to aLFUS control apparatus to enable an operator control of the function ofthe LFUS transducer of the multifunction system. A selectable dutyfactor between 1% and 100%, plus a selectable intensity level of between0.5 W/sq. cm and 25 W/sq. cm is provided to the operator via the LFUScontrol apparatus. The preferred LFUS treatment waveform comprises afrequency of 27 kHz, with a 100% duty factor emission at maximumtolerable intensity by the patient 20 in emergency situations. Atemperature probe (not shown) is optionally attached to the periphery ofthe engagement face of the variant ultrasonographic imaging and LFUStreatment contact (which equates to the active contact surface of theprovided ultrasonic phased array Imaging transducer) in order to supplya readout such that the operator can adjust the duty factor and/orintensity levels of the LFUS treatment when (or if) the temperature atthe tissue interface rises to an unacceptable level to avoid burning ofthe skin of the patient 20. Alternatively, the variant ultrasonographicimaging and LFUS treatment contact may be exchanged, with theapplication skin surface cooled down by a wash cloth or ice bag inbetween variant ultrasonographic imaging and LFUS treatment contactexchanges. In this multifunction system embodiment, noninvasive lowfrequency vibration (i.e. in the sonic to infrasonic range), lowfrequency treatment ultrasound, and high frequency ultrasonic imagingare utilized nondestructively in concert (i.e. simultaneously) toprovide an optimized therapy system for acute vascular obstructions andtreatment of ischemic events, optimally employed as an adjunct tosystemically delivered drug therapy, to improve localized drugeffectiveness.

It should be understood that while the low frequency vibration source tothe multifunction system advantageously comprises the active componentsof preferred vibrator 10 (i.e. to enable a high degree of low frequencyvibration control), this selection of low frequency vibration source Isnot critical to enable use of the multi function system according to theinvention, and any known vibration source operable to generate vibrationwithin the 1-1000 Hz range (so long as the therapeutic vibration waveform does not disable or interfere with the necessary ultrasonic imagingwave form, or therapeutic low frequency ultrasonic wave form) may beused, regardless of the level of provided vibratory emission control.Such vibration sources may for example comprise, but not be limited to:linear stepper motors, linear stepper motors with displacementamplification, linear (non stepper) motors, ceramic servo motors coupledto either a rotary (with cam) or linear stage, rotary motors with rotaryto linear conversion elements, eccentrically spinning weights,magnetostrictive linear motors, voice coils, and shakers (e.g. with orwithout neodymium magnet transducers).

Furthermore, it should be understood that the type of LFUS transducer ofthe multifunction system may be varied and a magnetostrictive actuatoroperable within the 20-100 kHz range may be used in the stead of theprovided piezoelectric actuator. Also, while the embodiment shown (i.e.apparatus) provides a “variant ultrasonographic imaging and LFUStreatment contact” with an end to end acoustic coupling between theprovided LFUS transducer and provided ultrasonic phased array imagingtransducer (i.e. such that the emitted LFUS wave form is transmittedthrough the active components of the ultrasonic phased array imagingtransducer), alternatively other structural variations are possible toenable use of the multifunction system. For example, an ultrasonicimaging transducer may be disposed around or alternatively placed sideby side to an incorporated LFUS transducer, such that the active ends(or engagement faces) of both units are directly adjacent to one anotherand thereby sharing a common application surface for contact to thepatient 20. Treatment applicators of similar design to this arediscussed in U.S. Pat. No. 5,558,092 to Unger et al., incorporatedherein by reference. The relative geometry (i.e. ultrasonic imagingtransducer disposed about the LFUS transducer (or vice versa) and therelative contact surface areas of the two complimentary engagement facesare not critical, as long as both the active contact surface of the LFUStransducer and the active contact surface of the ultrasonic imagingtransducer are represented to a sufficient degree to enable theirrespective functions, and are placed in close proximity to one another.Preferably the shared contact surface provided would be of a size, andshape, to enable efficient seating in a rib space of the patient 20, tooptimize use in transthoracic applications.

As the cost of incorporation of an ultrasonic phased array imagingtransducer to enable ultrasonic imaging for low frequency vibrationdirected therapy may be prohibitive in some medical centers, a more costeffective LFUS therapy concurrently with the transmission of lowfrequency vibration therapy (i.e. a “dual therapy”), withoutultrasonographic imaging capabilities is provided. This “dual therapy”option to the present invention comprises a variant “LFUS treatment”contact (not shown), adapted for removable attachment to shaft 16 ofvibrator 10 (or provided variants thereof), wherein a semi sphericalsilicone dome advantageously attaches and partially encapsulates adistal, active end of a low frequency ultrasound transducer which isoperational at 27 kHz (although any low frequency ultrasonic transduceroperational within the 20-100 kHz range, which is adaptable in size andshape to enable seating within a rib space may be used. A rectangularslit is centered at the semi spherical silicone dome's curved contactsurface to provide for a minimal protrusion of the distal, activesurface of the low frequency ultrasound transducer's distal, active endwhich is advantageously slide-ably engaged there through. Thisarrangement enables stable contact of both the distal, active surface ofthe low frequency ultrasound transducer and the curved contact surfaceof the silicone dome, such as to enable optimal transmission of lowfrequency vibration and the LFUS therapeutic signal to the chest wall(i.e. within the rib spaces) and/or other body part treated. Optionally,the distal, active surface of the low frequency ultrasound transducer isadapted in size and shape, such as to seat uniformly within a selectedrib space of the patient 20, and thus eliminating the need of anaccompanying silicone dome, which serves only to optimize seating andtransmission of the low frequency vibration aspect of the dual therapy.The non-active “proximal” end of the variant LFUS treatment contact thehousing for the electronic components of the provided low frequencyultrasound transducer, wherein a hollow connecting column is attachedwhich enables removable attachment of variant LFUS treatment contact toshaft 16 of vibrator 10 (or provided variants thereof). In this LFUSdual therapy option, shaft 16, once activated, vibrates the connectingcolumn which thereafter vibrates the housing for the electroniccomponents of the low frequency ultrasound transducer, which in turnvibrates the attached distal, active surface of the low frequencyultrasound transducer and the attached silicone dome, which takentogether, comprises the variant LFUS treatment contact. The simultaneousdelivery of a low frequency ultrasonic wave form and low frequencyvibration therapy (i.e. in the sonic to infrasonic ranges) via a commonapplication surface is thus enabled.

Alternatively, in a variant assembly, a pair of LFUS treatment contactsare slide-ably and lock-ably mounted along the length of a variantbifurcated connector (not shown), such as to enable bridging of thesternum of the patient 20, as per the preferred method of attachment incardiac applications. In still-another variant assembly, a pluralitybeyond a pair of LFUS treatment contacts may be employed to enableplacement to a plurality of intercostal spaces.

Like in the aforementioned “multifunction system” a selectable dutyfactor of between 1% and 100%, and selectable intensity level of between0.5 W/sq. cm and 25 W/sq. cm, is provided to the operator via a LFUScontrol apparatus in the LFUS dual therapy system. A temperature probeplaced at the periphery of the active contact surface of the lowfrequency ultrasound transducer (i.e. wherein the active contact surfaceinterfaces with the skin of the patient 20) is optionally provided witha readout, such that the operator can adjust the duty factor andintensity levels when (or in the temperature at the tissue interfacerises to an unacceptable level to avoid burning of the skin of thepatient 20. Alternatively, the variant LFUS treatment contact may beexchanged, with the application skin surface cooled down by a cool washcloth or ice in-between variant LFUS treatment contact exchanges.

The provided low frequency ultrasound transducer in the dual therapyvariation employs a piezoelectric actuator, however alternatively amagnetostrictive element (preferably operational within the range of20-100 kHz), may be used to enable the method and dual therapy system.It should also be understood that while the embodiment shown (i.e.apparatus—the LFUS treatment contact) preferably incorporates the use ofa partially encapsulating structure with a slit disposed about theprovided low frequency ultrasound transducer, this arrangement is notcritical and the low frequency ultrasound transducer may be optionallyapplied alone (or by any other means), directly to the skin surface ofthe patient 20, without such an accompaniment. In this “dual therapy”option, low frequency vibration (i.e. in the sonic to infrasonic range)and low frequency ultrasound (without high frequency ultrasonic imaging)are utilized nondestructively in concert to provide an optimized therapysystem for acute vascular obstructions and ischemic events, optimallyemployed as an adjunct to systemically delivered drug therapy to improvelocalized drug effectiveness.

In the preferred embodiment, (which utilizes low frequency vibrationsolely in the sonic to infrasonic ranges), vibrator 10 is secured topatient 20 by the hand or hands of an operator, wherein an alternativemeans of engagement employs use of clamp 100.

Referring now to FIG. 11, a perspective view of a variation of clamp100, namely “clamp 101” is shown. Clamp 101 is used to attach vibrator10 to the chest wall for cardiac applications or for any body part. Theclamp 101 is made of steel, but may alternatively be made of aluminum orany other suitable material which can supply sufficient strength andstiffness to maintain the necessary position of vibrator 10 andapplication force to patient 20. Clamp 101 optionally comes with board104, which can slide underneath a supine patient's back. Base 102 ispreferably placed on top of board 104. A vertical hollow bar 103 extendsat substantially 90 degrees from base 102. An extendable arm 105 extendshorizontally from hollow bar 103, and can be slide-ably moved up anddown hollow bar 103 to accommodate different sizes for patient 20. Oncepositioned extendable arm 105 is locked in place to hollow bar 103 withlocking knob 107, however other mechanisms such as a clip or notch maybe used. Extendable arm 105 in this variation is non-rotatable about thelongitudinal axis of hollow bar 103 and advantageously comprises anangle bracket to provide a more stable platform for vibration therapy.Weight 114 is optionally placed on extendable arm 105 to add furtherinertia to clamp 101 if required. Sleeve 116, which articulates with andsupports vibrator 10, is slide-able along extendable arm 105. Sleeve 116includes locking knob 109, which tightens to lock vibrator 10 in placealong extendable arm 105. Vibrator 10 is selectively lowered and raisedwith engagement screw 110, which articulates with and verticallytransverses sleeve 116 via a vertical screw column (not shown).Engagement screw 110 comprises an upper end disposing a turning knob,and a lower end that attaches the proximal, non-active end of housing 14of vibrator 10. Set screw 119 is provided to abut against engagementscrew 110 thereby locking it in place during operation. Rotatablecircular piece 118 in articulation with the lower end of engagementscrew 110 and disposed at the surface within the non-active end ofhousing 14 is provided such that housing 14 may remain stationary whileengagement screw 110 screws vibrator 10 up or down. The exact dimensionsof the components of clamp 101 (or 100) are not critical, as the heightof the vertical support of vibrator 10 and the horizontal distance ofvibrator 10 along extendable arm 105 (and arm 108) is made adjustable.

The force of engagement of vibrator 10 is optionally evaluated by astrain gauge force meter (not shown) or in a variation a weight scale(not shown). Optionally, a pivoting, rotating and locking universaljoint (not shown), located at the juncture between the non-active end ofthe housing 14 and the lower end of engagement screw 110, allows for theadjustment of the correct angulation and orientation of vibrator 10relative to engagement screw 110, to ensure a perpendicular contactbetween the attachment point of the contacts 12 and the chest wall (orother body part treated), wherein the patient 20 may not always restperfectly supine or lying flat. Universal joint adjustments comprisingangulations of less than or equal to 20 degrees (i.e. from the axis ofthe engagement screw 110) are recommended to ensure structural stabilityof clamp 100 or 101 engagement of vibrator 10 to the selected treatmentbody surface of the patient 20.

In both the clamp 100 and 101 variation of engagement, an emergencyquick release system comprising a mechanical lever (not shown) disposedto the underside of sleeve 116 is provided such that the screw columnwhich is internalized within the vibrator sleeve 116, can be quicklydisengaged by the mechanical lever from engagement screw 110, thus (oncequickly releasing set screw 119) liberating vibrator 10 from the patient20. Alternatively, a quick unlocking and detachment means (not shown) ofvertical bar 106 (and/or hollow bar 103) and the horizontal arm 108(and/or extendable arm 105) may be provided in the clamp 100 and 101variation, to allow an alternative means of quick release. An electricalshutoff switch (not shown) is provided to both clamp 100 and 101, incase of emergency.

Referring now to FIG. 12, a belt 130 variation of attachment means tothe chest wall of the patient 20 is shown wherein patient 20 is (in thiscase) sitting upright in Fowler's position (emergency use of IV's, nasalprongs and monitoring equipment according to the preferred embodiment isnot shown). Belt 130 is comprised of semi-flexible poly carbonateplastic, selectable in various curves to accommodate varying sizes ofchest for patient 20. The polycarbonate material may optionally betransparent. Alternatively, belt 130 may be comprised of any otherflexible material, which is highly resistant to longitudinal strain(such as reinforced leather, nylon or vinyl). Belt 130 is adapted tooverly substantially flat central panel 132, which is made lightweightand stiff in material and design. Central panel 132 is located to matchan area on the chest of patient 20 over the sternum. Central panel 132is provided in various sizes to accommodate different chest walldimensions and will optimally cover the 2nd to 6th intercostal spaces ofthe patient 20. The distal, cone shaped, active end of housing 14 ofvibrator 10 is attached and stabilized through slit 133 within centralpanel 132, having sides defined by a series of holes with semicircularedges, such that the vibrating attachment surfaces of contact orcontacts 12 of vibrator 10 make contact with the target site or sites(not shown in FIG. 12) on the patient 20. Slit 133 within central panel132 has beveled edges (not shown) which taper inwards towards patient 20to match the beveled distal active surface of the conical head ofhousing 14 of vibrator 10. Central panel 132, by means of the operatorselecting the appropriate location in slit 133, will allow for variableplacement of housing 14 of vibrator 10 and contact or contacts 12 todiffering intercostal spaces according to the optimal placementestablished by the operator (according to the methods describedearlier). Belt 130 covers the central panel 132 and partially encirclesthe torso of the patient 20 such that the ends of belt 130 extend up toand not beyond the front side of the mid-axial line of the patient 20(or, in other words, up to and not beyond the anterior half of the torsoof patient 20). Alternatively, in the flexible belt 130 variations, belt130 is preferably longer and is adapted to substantially encircle thetorso of the patient 20. Central panel 132 further includes a means ofsecuring vibrator 10 comprising slide-able and insert-able bolts (notshown) adapted to snap into corresponding slots (not shown) located atthe distal, active end of housing 14 to thereby lock vibrator 10 inplace. Belt 130 further comprises matching (but slightly larger) beltslit 135 to slit 133 in central panel 132, to further cradle the beveleddistal active end of the housing 14 of vibrator 10, such that theproximal, non active end of housing 14 is projected away from thepatient 20. The securement means of belt 130 to the backside of thepatient 20 is enabled through utilization of a bungee cord (not shown),which is selectable in varying lengths and diameters. The providedbungee cords have ends comprising metal hooks, which are made securableto reinforced holes (not shown) placed near the ends of belt 130.Optionally, the securement means of belt 130 may comprise any highlyelastic material which allows for an appropriate degree of strain andrecoil under load, in order to allow for expansion of the chest of thepatient 20 during inspiration while still maintaining adequate tensionto belt 130 and thereby maintaining adequate engagement force (i.e. atleast 5-10 N, preferably 20-100 N, and optimally 50-100 N) to centralpanel 132 (and thereby vibrator 10) to enable the application ofvibration therapy regardless of phase of respiration of the patient 20.Fine tuning of the engagement force to the chest wall of patient 20 isprovided to the operator by an inflatable bladder (not shown) which isremovably placed (while deflated) to the underside of the securementmeans of belt 130, preferably to the hollow between the shoulder bladesof the patient 20 once the bungee cord securement (or variation thereof)is secured in place. The operator (which may in this case be or includethe patient 20) incrementally inflates (or deflates) the inflatablebladder until the desired engagement force of vibrator 10 to the chestwall of patient 20 is achieved (i.e. about 10-20 N, and preferably about20 N in expiration, and less than or equal to about 100 N ininspiration).

A force meter (not shown) is also optionally provided to determine andmonitor engagement force of contact or contacts 12 against the chestwall (or other body part) of the patient 20. The maximum engagementforce tolerable to the patient 20 is recommended, so long as vibrator 10does not dampen (or stop) its oscillations from too great an engagementforce, and the patient 20 can breathe freely, and tolerate the vibrationtherapy within a determined or predetermined safety limit). Belt 130once secured with adequate tension, will provide appropriate engagementforce to central panel 132, which in turn supplies appropriateengagement force to vibrator 10, (and contact or contacts 12—not shownin FIG. 12) to enable the application of vibration therapy to the chestwall of the patient 20, or alternatively the backside or any body partof patient 20.

The design of belt 130 is advantageous as the patient 20 when nauseousmay sit up or roll over during vibration therapy.

Variant securement means of belt 130 to the backside (or contra lateraluntreated side) of the patient 20 is obtained by a resilient,substantially inelastic pair of Velcro™ straps (not shown), but may as afurther variant comprise a pair of like securement straps with holesconnected by a tang (not shown), or as a further option a pair ofsecurement straps connected by a tightenable friction buckle (notshown). In this resilient, substantially inelastic variant securementsystem (which is preferable for body parts which do not substantiallychange size or shape), the same bladder, (which has a greater lengththan the securement strap's width) is removably centered to theunderside of the secured inelastic straps, once the straps are fastened.Again placement of the bladder is preferably to the hollow of the backbetween the shoulder blades of the patient 20 for chest wallapplications, or to the contra lateral (or diametrically opposed)untreated side to the body part treated. In addition to the provision ofa control means for engagement force, the bladder (which is made of asemi compliant material), will buckle slightly at the securement sitewhile under load hence providing a degree of compliance to the otherwisesubstantially non yielding variant securement means which (unlike thepreferred bungee cord rubber securement means) is highly resistant tolongitudinal strain, thereby enabling the chest of the patient 20 toexpand and relax with respiration in transthoracic applications. Theadvantage to the Velcro™ straps variant securement system, while lesscompliant and thus offering less comfort to the patient 20 duringinspiration in transthoracic applications, is that it provides for themost stable platform to central panel 132 for engagement of vibrator 10to the chest wall (or any other body part treated).

Other variations to the engagement system of belt 130 such as a halter,strap, sling or vest (i.e. for sitting up or ambulation), may be adaptedto the present invention by those skilled in the art of vibration orpercussion garment manufacture, to enable support and necessaryengagement force for the relatively high amplitude vibration therapy tobe applied to the anterior chest wall of the patient 20 while in anupright position. The present invention provides a set of removable, andlength adjustable shoulder straps (not shown) which connect with belt130 via reinforced alligator clips, such as to provide vertical supportto belt 130 engagement when the patient 20 is in the upright position.Alternatively, any other commercially available or adaptable means ofshoulder strap attachment is acceptable. The garment variations willallow fixation of vibrator 10 (or provided variant) to the target siteupon the anterior region of the chest wall (i.e. overlying themediasteinal cavity), while allowing patient 20 movement or evenambulation during vibration therapy.

It should be understood that the above described variation of engagementmeans for belt 130 (and all variations thereof) can be utilized oradapted for any body part, and not just to provide engagement to thethorax of the patient 20, and may also be adapted to provide support toother suitable vibrators (or percussion instruments by other name), andnot just the preferred vibrator 10 (or provided variations thereof).

Mobile, Emergency Response System for Paramedic Use:

For first line response by paramedics in an ambulance or beforetransportation, a self-contained, mobile, emergency, response kit forthe treatment of acute, thrombotic and/or vasospastic vascularobstructions, including a selection of drugs, drug delivery supplies,and the preferred vibrator 10 (with a selection of attachment interfacesto enhance vibration transmission and effectiveness) is provided. Themobile, emergency response kit may also be employed by nurses and/orphysicians in the Emergency room, upon arrival of the patient 20 tohospital. The preferred application is for acute coronary vascularobstructions, yielding a diagnosis of Acute ST elevation MyocardialInfarction.

The mobile, emergency response kit includes:

a) Vibrator 10 (with bifurcated connector 13 and a set of removablyattached contacts 12 of varying size),

b) Portable, compartmentalized storage carrying case,

c) Drugs,

d) Drug delivery supplies,

e) Portable high powered DC battery pack, (operational with vibrator10),

f) A pair of sleeves 23 (each sleeve 23 incorporating an additional pairof support arms 22) for optional attachment to bifurcated connector 13,

g) Variant Connector 19 with a pair of variant sleeves 27,

h) Variant non bifurcated connector,

i) Variant ultrasonographic imaging contact 60, and portable ultrasonicimaging device plus ultrasonic conducting gel, and

j) Xylocalne 2% (for optional freezing of the skin surface treated).Optional provisions for the mobile, emergency response kit include:

a) Clamp 100 (engagement means),

b) Variant clamp 101 (engagement means),

c) Belt 130 system (engagement means),

d) Variant LFUS treatment contacts with variant bifurcated connector andLFUS control apparatus,

e) Variant ultrasonographic imaging and LFUS treatment contact with LFUScontrol apparatus,

f) Variant peripheral contact heads with semi malleable attachmentinterface,

g) Cardiac phase controlled vibration delivery system comprising;variant cardiac phase controlled vibrator 11 (“variant 1”), ECGmonitoring system 36, variant processor 35, display monitor 52, variantinterface 51, and external accelerometer 39,

h) Variant research vibrator (“variant 2”),

i) Variant light weight vibrator (“variant 3”),

j) Variant heavy duty vibrator (“variant 4”),

k) Larger, portable, compartmentalized storage carrying case, and

1) Set of helmet attachment means comprising helmets of various sizes.

The preferred vibrator 10 for the mobile, emergency response kit isoperable to emit vibration within the 1-120 Hz range, and provides aselection of displacement wave form emissions (i.e. sinusoidal, square,saw tooth, and exponential waves), with a maximum displacement amplitudeof up to 15 mm. Vibrator 10 is operational under engagement forces of upto about 100 N, such as to enable a high energy, deeply penetratingemergency system of vibration therapy. Vibrator 10 runs on AC power viaa power cord, or alternatively by battery power via a high poweredremovable and interchangeable DC battery pack.

The variant research vibrator (“variant 2”) is of optional inclusion tothe mobile emergency response kit, and offers a higher range ofvibration frequencies within the range of 1-1000 Hz. The variantresearch vibrator (“variant 2”) has a limited displacement amplitudeenablement (i.e. in the low millimeter to sub millimeter ranges) and isprimarily used for research purposes (i.e. in the 150-1000 Hz range)and/or use with variant ultrasonographic imaging contact 60 for directedvibration therapy. Also, the variant light weight vibrator (“variant3”), and the variant heavy duty vibrator (“variant 4”), are bothoptionally included. The variant heavy duty vibrator is particularlyeffective in cases where high engagement forces are required to ensuretherapeutic penetration, such as when the patient 20 is obese, or whenthe upper back (or posterior thoracic region) of patient 20 is utilizedas an application site (as described earlier). The variant light weightvibrator (“variant 3”) is preferable if the patient 20 is utilized toengage the device, or self administer the vibration application.

The mobile, emergency response system comprises a self contained system,employing a module and portable storage carrying case (not shown) whichhouses the components of the mobile emergency response kit. A variantlarger portable storage carrying case (not shown) is adapted toadditionally house optional components.

The mobile, emergency response system enables systemic drug delivery,via intravenous, intra arterial, subcutaneous, oral, topical and nasaldrug administration means. Drugs within the mobile, emergency responsekit include: thrombolytic agents (e.g. ACTIVASE™ (Alteplase), TNKase™(Tenecteplase), RETAVASE™ (Reteplase), Abbokinase™ (Urokinase),Kabikinase™ (Streptokinase with water), Streptase™ (Streptokinase with0.9% NaCl solution), Lanoteplase); GP 2b 3a platelet inhibitors (e.g.ReoPro™ (Abciximab), AGGRASTAT™ (Tirofiban hydrochloride), Integrelin™(Eptifibatide)); calcium channel blockers (e.g. ISOPTIN™ SR (VerapamilHCl), ADALAT XL™ (Nifedipine), Cardize™ (Diltiazem), NORVASC™(Amlodipine besylate); Nitrates (Nitroglycerine (spray, pill or patch),isosorbide dinitrates (Isordil™ and Sorbitrate™), Nipride™(Nitroprusside); Oral anti-platelets (e.g. Acetylsalicylic Acid(Aspirin), Plavix™ (Clopidogrel), TICLID™ (Ticlopidine hydrochloride);Anti-coagulants such as heparin; and concentrated oxygen. It should beunderstood that the mobile emergency response kit may contain any one ofthe above listed drugs, or any number of the above listed drugs in anycombination.

Non-pharmacological “drugs” such as echo contrast agents (i.e. microbubble solutions which lower the cavitational threshold of a medium),which may be delivered systemically along with other IV drugs, areoptionally included in the mobile, emergency response kit to enhance theagitative internal effects of externally delivered vibration therapy.Optional cavitating micro bubble solutions within the mobile, emergencyresponse kit include: EchoGen™ (Dodecafluoropentane emulsion), Albunex™(5% human albumin), LEVOVIST™ (Galactose Palmitic Acid ultrasoundcontrast agent), Air containing albumin microcapsules (Quantison™ andMyomap™), SonoVue™ (Sulfurhexafluoride) and Perfluorocarbon containingmicrobubbles (Perfluorocarbon exposed sonicated dextrose albumin PESDA).Cavitating microbubbles solutions are particularly effective inconjunction with joint LFUS administration, and are readily implementedin conjunction with use of the variant LFUS treatment contacts, orvariant ultrasonographic imaging and LFUS treatment contact, as per the“dual therapy” or “multifunction system” methods of LFUS administrationas described earlier.

Drug delivery supplies within the mobile, emergency response kitinclude: IV tubing, IV start kits, sterile IV introduction needles,tape, IV pole, 0.9 NaCl IV solutions, Dextrose IV solutions, Code 8 IVsolutions, Heparinized IV solutions, IV pressure bag with pressure gaugeand pressure bulb, sterile intra arterial introduction needles, guidewires, sheaths with dilators, scalpel blades, one way stopcocks, threeway stop cocks, sterile drapes, sterile gowns, sterile gloves, sterileskin preparation solution, needles adapted to subcutaneous drugdelivery, alcohol swabs, paper cups, straws, sublingual sprays, aerosolsprays, oxygen tank, ambubag, oxygen tubing, oxygen mask, and nasalprongs. It should be understood that the mobile emergency response kitmay include any one of the above listed drug delivery supplies, or anynumber of the above listed drug delivery supplies in any combination.

The variant ultrasonographic imaging contact 60 (with a portable handcarried ultrasonic imaging device—not shown), is also provided to themobile, emergency response kit, so a skilled operator (when available)can optionally establish a viable sonic penetration window and targetthe culprit vascular region (directly or by anatomic reference) with lowfrequency vibration with optimal efficiency. Variant ultrasonographicimaging contact 60 is readily adaptable for use in all providedvariations of vibrator 10 (i.e. as per the “optional provisions” listedabove), and is of preferred use when a trained operator is available,and with the variant research vibrator (“variant 2”), whereby a directedapproach for higher frequency lower displacement amplitude vibration(i.e. above 150 Hz) is generally required to ensure therapeutic levelsof penetration to the culprit region targeted.

The variant ultrasonographic imaging and LFUS treatment contact is alsooptionally provided to the mobile, emergency response kit to enable theapplication of ultrasonic imaging, low frequency vibration, and lowfrequency ultrasound (as a second therapeutic wave form) simultaneouslyand in concert via the multifunction system (as previously described).For cost effectiveness, a pair of variant LFUS treatment contacts (withvariant bifurcated connector), enabling emissions of low frequencyultrasound without imaging capabilities (i.e. without the use of arelatively expensive incorporated ultrasound imaging transducer—as perthe “dual therapy” option) is also optionally provided. The IV or IAadministration of cavitating microbubbles, with or without other helpfuldrug agents (e.g. as per the methods disclosed in U.S. Pat. No.5,695,460, said being incorporated herein in toto by this specificreference thereto) are recommended as an adjunct low frequency vibrationand joint LFUS wave form delivery.

The cardiac phase controlled vibration delivery system is optionallyincluded within the mobile, emergency response kit for treatment ofAcute Myocardial Infarction complicated by cardiogenic shock. A cardiacphase “mode” selection enables cardiac phase dependent vibrationdelivery, wherein “mode” defines the timing of emission of vibrationtherapy according to cardiac phase (i.e. systole vs. diastole). Theselection of vibration mode enables the application of vibrationspecifically during the diastolic phase of the cardiac cycle, which isuseful in AMI cases which have deteriorated to cardiogenic shock asdiastolic vibration, besides agitating and assisting dissolution of theculprit coronary obstruction, is also known to provide a positiveinotropic effect. The provided cardiac phase dependent vibrationdelivery system is optionally programmable to enable the selection ofvarying frequency of vibration according to cardiac phase. It isadvantageous to for example vibrate the myocardium between 20-60 Hz (andoptimally 50 Hz) during ventricular diastole (approximating thediastolic resonance frequency of the myocardium) and to vibrate themyocardium between 70-120 Hz (and optimally 100 Hz) during ventricularsystole (thereby approximating the systolic resonance frequency of themyocardium which is stiffer in systole). Higher frequencies at samedisplacement amplitude are generally known to improve blood clotdisruption and induce cavitation and acoustic streaming, thus takingadvantage of the myocardium's higher vibration resonance frequencyduring the systolic period (or debatably at any time throughout thecardiac cycle) is advantageous.

For the sake of simplicity and ease of portability, the mobile,emergency response kit of the present invention incorporates only themandatory elements to enable the aforementioned cardiac phase controlledvibration delivery system wherein ECG 36, variant processor 35, variantinterface 51, display monitor 52, external accelerometer 39, and variantcardiac phase controlled vibrator 11 (“variant 1”), is all that isutilized to enable cardiac phase controlled vibration delivery. Thedeflection of the QRS complex from ECG 36 is interpreted by variantprocessor 35 (which defines the timing of the onset of “ventricularsystole”), and a rate related timing delay is thereafter appliedfollowing the QRS complex (which defines the timing of the onset of“ventricular diastole”). Variant processor 35 is thereby enabled torespond to operator inputted cardiac phase modulated vibrationalgorithms and therein provide output commands to variant cardiac phasecontrolled vibrator 11 (“variant 1”), to enable the delivery of cardiacphase dependent time and optionally frequency varying vibration therapy.The operator, upon viewing the ECG 36 and accelerometer 39 output on thedisplay monitor 52, can adjust (or fine tune) the timing of vibrationemission via the variant interface 51. Ideally diastolic vibrationshould commence from the terminal end of the T wave, and thendiscontinue upon the onset of the deflection of the QRS complex asvisualized by the provided ECG 36 wave form. As stated the use of the“advanced method” is of significant importance when the patient 20 issuffering from an acute coronary vascular obstruction which hasdeteriorated to a state of cardiogenic shock.

In a variation, the variant cardiac phase controlled vibrator 11 may beadapted to provide a self contained operator held unit (i.e. completewith control means, processing means, display means, cardiac phasemonitoring means, and vibration timing indication means—as describedearlier), such as to enable a more easily portable and expedited cardiacphase controlled vibration delivery system to the mobile, emergencyresponse kit.

Further options to the mobile, emergency response kit include anengagement means (i.e. clamp 100 or clamp 101, and/or belt 130 system)so that an operator need not hold vibrator 10 (or provided variant) byhand throughout the course of vibration therapy. A retractable IV stand(not shown) is optionally incorporated within and extending from bar 106of clamp 100. In another variation of clamp engagement, bar 106 (i.e. inclamp 100) and/or hollow bar 103 (i.e. in clamp 101) may be placed andsupported directly to the stretcher of the patient 20 by a vice grip orother locking mechanism (i.e. rather than to base 102), or, arm 108(i.e. in clamp 100) and/or extendable arm 105 (i.e. in clamp 101) may bealternatively supported by a portable unit with lockable wheels ordirectly to a wall or fixture in the emergency room or within theambulance.

It should be understood that while the mobile, emergency response kitadvantageously employs the preferred vibrator 10 (such as to enable ahigh degree of operator enabled vibration emission control), thisemployment (or choice of vibrator 10) is not critical in the mobile,emergency response system and alternatively any known (or adaptable) lowfrequency (i.e. operational in the 1-120 Hz range) vibrator (orpercussion, or oscillation device by other name), with a suitableattachment interface for selected body surface contact (preferablyenabling concentrated delivery of vibration between the rib space orspaces of the patient 20), being operable at high displacementamplitudes (i.e. >2 mm, and preferably >4 mm deflections) and engagementforces (i.e. >5-10 Newtons, and preferably >20 Newtons), mayalternatively be used, regardless of the level of operator enabledvibration control.

It should similarly be understood that cardiac phase controlledvibration delivery according to the mobile, emergency response systemmay be embodied (by apparatus) in many ways, and should not berestricted to the system herein described. Any low frequency vibrator(or vibration system), preferably operable at a high displacementamplitude (i.e. greater than 2 mm and preferably greater than 4 mmdeflections) and high engagement forces (i.e. at least 5-10 N, andpreferably greater than 20 N), which is adapted to provide cardiac phasecontrolled vibration delivery (i.e. with vibration timing emissionalgorithms and optionally vibration frequency algorithms) may be used.The apparatus may comprise a plurality of separately located elements(as provided), or may alternatively comprise a single, self containedoperator held instrument (as described earlier).

Referring now to FIG. 13, the preferred method of employment of thevibrator 10 (or percussion device by other name) for treatment of acutevascular obstructions is schematically shown. Step (A) comprises thestep of systemically administrating at least one and preferably aplurality of useful drugs adapted for treatment of an acute vascularobstruction which is usually a combination of thromboses and vesselspasm. Such drugs may include but not be limited to thrombolytics, GP 2b3a platelet inhibitors, nitrates, anti coagulants, oral anti-platelets,concentrated oxygen and morphine. Step (B) comprises the step ofapplying vibration to a selected or pre-determined external body surfacedeemed proximate the acute vascular obstruction via the preferredvibrator 10 (or other suitable percussion device as described above).Application by vibrator 10 is preferred in the case where the operatorhas no specialized skill or training in ultrasonic imaging (which wouldbe the most common scenario in the field or in the ER). Engagement tothe anterior chest wall bridging the sternum is shown (which ispreferred in acute myocardial infarction cases, although the backside ofthe patient and other areas upon the chest wall may also be utilized),and ideally the highest force or displacement amplitude deemed safe andtolerable to the patient 20 is selected to ensure optimal penetrationand effectiveness of the percussive signal. Step (D) comprises theprovisional step of employing diastolic timed vibration via the cardiacphase controlled vibration delivery system (or any suitable variationthereof) in the special case wherein the patient 20 deteriorates into astate of cardiogenic shock or cardiac failure, which is not uncommon inacute myocardial infarction cases. Diastolic timed vibration is known toreduce LV diastolic pressures and promote a positive inotropic effect toLV function. Otherwise “continuous” vibration may be continued ordiscontinued in accordance to a risk/benefit decision by a responsibleoperator. It should be understood that the initiation of vibration (B)may proceed or be concurrent with the administration of drug therapy(A). Furthermore, it should also be understood that vibration therapy(B) may alternatively be utilized alone without adjunctive drug therapy(A), such as in the special cases whereby drug therapy is not indicated(i.e. for patients with substantial bleeding risks or other co-morbidfactors), drug therapy is not available (i.e. at home or in the field),wherein drug therapy is not allowed or not authorized (e.g. patientrefusal, or in the case where the operator is not authorized to givedrugs), and/or wherein drug therapy is not preferred or not prescribed.

In reference to FIG. 14, a variation to the preferred vibration methodincorporating the employment of ultrasonic imaging to direct vibrationis shown. Step (A) comprises the same step of systemicallyadministrating a clot dissolving and/or vasodilatory drug to the patient20 as per the prescribed therapy. Step (C) comprises the step ofapplying and directing vibration by means of ultrasonic imaging (i.e.the variant dual function imaging vibration device 15 applied to patient20 is shown, however any suitable vibrator—as described above-coupled toan ultrasonic imaging transducer at its active end may be used). Thevariant dual function imaging vibration device 15 (or variation thereofis optimally placed and directed via ultrasonic imaging, to emitvibration towards an acute vascular obstruction targeted. This isaccomplished by either direct visualization (e.g. such as visualizationof a blood clot within a blood vessel) or by anatomic reference, whereinfor example placement in proximity to the base of the heart, andvisualization of the substantially akinetic, basal aspect of themyocardium wherein the culprit blood clot is likely to reside definespreferred placement and direction of vibration in acute myocardialinfarction cases. Step (D) comprises the optional step of employingdiastolic timed vibration via the cardiac phase controlled vibrationdelivery system (or suitable variation thereof) in the special casewherein the patient 20 deteriorates into a state of cardiogenic shock orcardiac failure. Again it should be understood that vibration therapydirected by ultrasonic imaging (C) may be independent of drug therapy(A), and may alternatively proceed or be initiated concurrently with theinitiation of drug therapy (A).

In reference to the application of the mobile emergency response kit inthe field, a tutored paramedic or physician, once arriving to thepatient 20 and establishing a diagnosis, preferably selects at least onedrug based upon clinical need and/or patient 20 bleeding risks,systemically administers the drug (or drugs), and then transcutaneouslyvibrates the body surface of the patient 20 deemed to overly the generalarea of the acute culprit vascular obstruction. As stated a skilledimaging approach to direct vibration may be employed if the operator hasthe skill and training required to recognize pertinent ultrasonicimages, otherwise the preferred vibrator 10 (or other suitablenon-imaging vibrator) with a pair or optionally a plurality beyond apair of contacts 12 should be utilized. Low frequency vibration in thesonic to infrasonic ranges (i.e. 1-120 Hz; preferably 20-120 Hz incardiac applications), or at any frequency within the 1-1000 Hz rangemay be used. Generally, the default frequency of 50 Hz sinusoidalvibration is preferred, as 50 Hz sinusoidal vibration can be deliveredat a relatively high displacement amplitude, has excellent penetrationcharacteristics through the chest wall and other body surfaces, fallswithin the resonance frequency of the heart, and is a well establishedfrequency known to produce vascular dilation, cavitation, and acousticstreaming for encouraged clot disruption and increased drug mixing andpermeation. Alternatively, square wave <b> (i.e. with a steepdisplacement rise for high impact, better penetration and disruptiveaction), saw tooth wave <c>, exponential wave <d> or any linear ornonlinear (or combination thereof) displacement wave form, may be used(see FIG. 8). Generally the maximum tolerable (and judged safe) force ordisplacement amplitude should be utilized in cases of acute myocardialinfarction or acute vascular obstructions to the pulmonary or peripheralvasculature, wherein cell death, and/or hemodynamic compromise isotherwise imminent. A gentle 1-2 mm displacement amplitude may bepreferable for the treatment of ischemic stroke (preferably viaapplication of the contacts 12 of vibrator 10 to the posterior,posterior lateral or lateral aspect of the neck of the patient 20 or viathe provided helmet attachment means) until a definite diagnosis ofischemic (or embolic) stroke is established, however higher treatmentamplitudes may be considered as first line treatment according to arisk/benefit weighted decision (i.e. risk of cerebral hemorrhage vs.benefit of accelerated reperfusion) made by the attending clinician, orafter the diagnosis of embolic stroke (i.e. vs. hemorrhagic) isestablished.

The patient 20 is transported to hospital or other treatment facility,preferably with vibration and drugs simultaneously delivered. Thevibration therapy preferably continues until clinical signs ofreperfusion are evident, or until an invasive corrective procedure suchas emergency PCI (i.e. in heart attack cases) is established.

Portable, Emergency Response System for Outpatient Use:

For first line treatment of a citizen in the community (e.g. before thearrival of paramedics), a self-contained, portable, emergency responsekit for the treatment of an acute thrombotic coronary vascularobstruction at early stage is provided. Components of the portableemergency response kit include the variant lightweight vibrator(“variant 3”), and preferably at least one anti anginal medication to bedelivered. The portable, emergency response kit is designed to beutilized by the patient 20 as an emergency tool for self administration(or assisted administration by a non-trained or indeterminately trainedbystander) within the community.

The portable, emergency response kit comprises a black leather portablecarrying case which is adapted to house and port: the variantlightweight vibrator <“variant 3”> (including bifurcated connector 13with a set of removably attached contacts 12 of various sizes), aportable DC power pack, an AC power cord, preferably at least oneanti-anginal medication (such as Nitro spray, Nitro pill, Nitro patch,Isordil™, and/or Sorbitate™), and optimally at least one oralantiplatelet medication (such as Acetylsalicylic Acid, Plavix™, and/orTICLID). A larger brown leather carrying case is adapted to additionallyhouse and port a small oxygen canister and nasal prongs to enable theadministration of concentrated oxygen to the patient 20, as well as asmall portable blood pressure device adapted to take blood pressure fromthe wrist of patient 20. The belt 130 engagement system (i.e. withinflatable bladder, bungee cord securement and, shoulder strapsupport-described earlier) may be provided so the patient 20 need nothold the unit by hand during the course of therapy. The patient 20 isinstructed to carry a cellular phone at all times to enable calling foremergency assistance when necessary. The use of the variant lightweightvibrator (“variant 3”) is preferable in the portable emergency responsesystem as the unit is light weight and easy to “self” apply by thepatient 20. As an option, the preferred vibrator 10 or variant heavyweight vibrator (“variant 4”) may be alternatively selected, or anyother low frequency commercially available vibrator (preferably offeringvibration displacement amplitudes of greater than at least 2 mm) may beused according to the preference of the patient 20.

Vibration therapy is, in this case, employed for acute states ofcoronary insufficiency with symptoms consistent with infarctionrefractory to nitroglycerine treatment in the patient 20, wherein anacute coronary thrombotic obstruction (i.e. “Heart Attack”) cannot beruled out. Every bout of chest discomfort that the patient 20 in thecommunity experiences might in fact be an acute coronary event wherein aplaque has ruptured and an acute thrombotic vascular obstruction hasoccurred.

The method of use of the portable emergency response system and kitcomprises maintaining the portable emergency response kit in proximityof the patient 20 at all times. When a symptom of “angina” is felt bythe patient 20 (i.e. chest pain or pressure, shortness of breath,nausea, diaphoresis, or “an impending sensation of doom”), patient 20should undertake anti-anginal medical therapy as prescribed by his orher physician. In these cases, the patient 20 will try the prescribedanti-anginal medication such as nitro spray*3 (i.e. with each dosespread 5 minutes apart), and upon recognition of no relief of chestdiscomfort (which may be quite severe), patient 20 will proceed to dial“911” wherein the diagnosis of an acute coronary thrombotic obstructionleading to an acute M1 cannot be ruled out until a professionaldiagnosis is obtained. As described earlier, hyper acute early clotformation at early stage is extremely amenable to dissolution viamechanical agitation, hence a mechanically disruptive, agitativetechnique such as the application of high amplitude chest wall vibrationtherapy as herein described, is prospectively an extremely effective andimportant first line emergency method and tool. The patient 20 will restand preferably additionally administer an oral antiplatelet medication(as above) as prescribed by a family physician or Cardiologist of thepatient 20. The patient 20 should articulate the potential medicalproblem of a potential “heart attack” to bystanders such that patient 20is not alone while waiting for the arrival of an ambulance andprofessional care (i.e. in the case of cardiac arrest). The variantlightweight vibrator (“variant 3”), or other selected vibrator is placedto the anterior chest wall preferably to bridge the sternum at thedefault level of the fourth intercostal space (although other attachmentconfigurations are possible as per the methods described earlier). Theblood pressure of the patient 20 may be monitored via the small portableblood pressure device, and oxygen may be administered until professionalassistance arrives.

The chest wall interface of the variant lightweight vibrator (“variant3”) is advantageously accomplished via the bifurcated connector 13,preferably equipped with preferably a pair of pre sized contacts 12,wherein the contacts 12 have been pre adjusted in location on supportarms 22 to optimally bridge the sternum and seat within the intercostalspaces of the patient 20 for maximum chest wall penetrability to thecoronary circulation as per the methods previously described.Optionally, variant connector 19 disposing two pairs of support arms 22(to enable four application sites via four contacts 12 to the patient20), or bifurcated connector 13 disposing an additional two pairs ofsupport arms 22 (to enable a total of three pairs of application sitesvia three pairs of contacts 12 to the patient 20) may be utilized formultiple intercostal space attachment, to enable maximal penetration oflow frequency vibration to the deeply situated and variably locatedcardiovascular regions within the thoracic cavity.

The vibration displacement amplitude is preferably selected as themaximum tolerable to the patient 20, who should ideally be resting ineither the supine position or seated comfortably in a chair. The optimalfrequency is selected at 50 Hz continuously applied vibration with asinusoidal wave form, however optionally any frequency within the 1-120Hz range, or preferably 20-120 Hz range (i.e. to match the resonancefrequency of the heart) and, square, exponential, or saw toothdisplacement wave forms may be optionally selected according to thepreference of the operator and/or prescribed therapy. Ideally a friendor bystander should engage the variant lightweight vibrator (“variant3”), or other provided vibrator against the patient 20 by hand untilprofessional care arrives. Alternatively, belt 130 with shoulder straps(or other variant garment, as described earlier) may be utilized, suchthat the patient 20 can self administer vibration therapy without theneed to exert any effort to hold the variant lightweight vibrator(“variant 3”), in place. The patient 20 will preferably administer adose of anti anginal medication such as nitro spray 0.4 mg SL (andoptionally an oral anti platelet agent), and then proceed to administeradjunctive vibration therapy (as per the methods disclosed earlier) suchas to provide a synergistic treatment system to assist localized drugeffectiveness to the coronary vasculature. Monitoring of the bloodpressure of the patient 20 (i.e. via the optimal small portable bloodpressure device) is advantageous as repeated dosing of nitroglycerine(or other nitrate employed) may be accomplished barring hypotensionduring vibration therapy.

As an option, the variant lightweight vibrator (“variant 3”), or otherselected vibrator, may be adapted to enable cardiac phase controlledvibration via the incorporation of an ECG monitoring system and suitableprocessing and control network (i.e. as a “self contained unit”—asdescribed earlier), such as to enable the application of vibrationrestricted to the diastolic phase of the cardiac cycle of the patient 20wherein it may be considered useful to provide a therapy which promotesa positive inotropic effect whereby the blood pressure and hemodynamicstatus of patient 20 may deteriorate (or will be unknown) untilprofessional care arrives. The ECG monitoring system in this case mayadvantageously comprise at least a pair of electrodes operativelyincorporated with or disposed upon at least a pair of contact surfacesof the utilized vibration attachment interface (e.g. which may forexample comprise the preferred pair of contacts 12 disposed uponbifurcated connector 13, or a plurality of contacts 12 wherein supportstructure 24 is utilized—as described earlier), such as to enable asimple and easy application means to the patient 20, without the botherof attaching electrocardiographic leads and so forth.

It should be understood that while the embodiment shown to the portableemergency response system (and kit) advantageously incorporates thevariant lightweight vibrator (“variant 3”), alternatively any known (oradaptable) low frequency (i.e. 1-120 Hz) vibrator (or percussion, oroscillation device by other name) of size and shape to enable hand heldoperation, with a suitable attachment interface for selected bodysurface contact (i.e. preferably enabling concentrated delivery ofvibration between the rib space or spaces of the patient 20), beingoperable at high displacement amplitudes (i.e. >2 mm, and preferably >4mm deflections) and engagement forces (i.e. >5-10 Newtons, andpreferably >20 Newtons), may alternatively be used. Such vibrationdevices should preferably be adapted to portable battery operation, toenable the application of vibration therapy in community wherein an ACwall outlet may not always be available.

It is significant that acute coronary thrombotic obstruction in thecommunity is one of the leading causes (if not the greatest cause) ofdeath in the civilized world today.

Many modifications are possible to the emergency system withoutdeparting from the spirit or innovative concept of the invention.

With regards to the vibration source of preferred vibrator 10, while theembodiment shown advantageously employs an electromechanical transducercomprising a high powered linear stepper motor (such as to enable a highlevel of vibratory control and selectivity of frequency, displacementamplitude and vibratory displacement wave forms), alternatively anyknown (or adaptable) low frequency (i.e. 1-120 Hz) vibrator (orpercussion device, or oscillation device by other name), with a suitableattachment interface for selected body surface contact (preferablyenabling concentrated delivery of vibration between the rib space orspaces of the patient 20), being operable at high displacementamplitudes (i.e. >2 mm, and preferably >4 mm deflections) and engagementforces (i.e. >5-10 Newtons, and preferably >20 Newtons), mayalternatively be used, regardless of the level of operator enabledvibration control.

For example, to achieve the same level of vibration control, a lowerstroke length enabled linear stepper motor (i.e. with a smaller statortube) in conjunction with a displacement amplifier may be used. Linearstepper motors of lower stroke enablement are more common andcommercially available, hence generally less expensive to employ.Alternatively, a high powered rotary stepper motor equipped with anexchangeable rotary to linear conversion element, or a specializedrotary to linear conversion element, (wherein the conversion elementindependently or in concert with the motor operation, enables adjustabledisplacement amplitude emission control) may be used. Conversionelements of this type are described (for example) in U.S. Pat. No.6,027,444 and U.S. Pat. No. 827,133 incorporated herein by reference.Furthermore, a rotary stepper motor configured to oscillate controllablyin an up and back manner along an arc of less than or equal to 180degrees (and preferably less than 120 degrees) in conjunction with a camor crank may be used to take the functional place of the provided“linear” stepper motor. Rotary motors are generally less expensive thanlinear motors. In yet a further variation, a ceramic servo motor coupledto a linear stage (as per modern, state of the art technology offered byNanomotion LTD, incorporated herein by reference), could be utilized toreplace the provided linear stepper motor, and provide virtuallyunlimited linear motion control.

For example, if only selectable displacement amplitude control isrequired, the electromechanical transducer may comprise any high poweredrotary motor interfaced with a specialized cam or crank, wherein the camor crank is exchangeable, or independently adapted to enable adjustabledisplacement amplitude control (e.g. as per technology in U.S. Pat. No.6,027,444 or U.S. Pat. No. 827,133 mentioned previously); a high poweredlinear motor of any type operational at a predetermined stroke coupledto a specialized linear conversion element which is adapted to enablevariable displacement amplitude control (such as, for example a leversystem with an adjustably located fulcrum); a ceramic servo motorcoupled to a linear stage (as above); or a linear stepper motor withoutthe enablement of varying displacement wave shape control.

For example, if only variable displacement wave form control isrequired, then any high powered rotary stepper motor with a rotary tolinear conversion element could be utilized. Alternatively, a ceramicservo motor coupled to a rotary stage (with rotary to linear conversionelement), or a ceramic servo motor coupled to a linear stage could beused. Furthermore, in the case high impact “pulsed”, or “square wave”vibration is desired (i.e. as a sole wave shape with a steepdisplacement rise per stroke—for deeper penetration and superiordisruptive action) a technology as per U.S. Pat. No. 5,951,501 or U.S.Pat. No. 6,682,496 may be used, (or any other known technology), whichutilizes a rotary motor with a specially engineered cam which isengineered to enable “striking” of a contact surface in a percussivemanner. It should be noted that if a “pure” sinusoidal displacement waveform is desired (i.e. as a sole wave shape-which has demonstratedsuperior vasodilatation characteristics) a rotary motor (of any type)with a rotary to linear conversion element such as a cam or crank may beemployed.

For example, if selectable “force” or “power” of vibration control (i.e.max force/stroke, and/or force wave shape control) is desired at a givenfrequency (as opposed to exacting displacement amplitude control and/ordisplacement wave shape control); a linear induction motor withadjustable force or power control, a linear permanent magnet motor withadjustable force or power control, a linear stepper motor withadjustable force or power control, a high powered speaker coil withadjustable power or volume control, a shaker with adjustable force orpower control, a ceramic servo motor coupled to a linear or rotary stagewith force or power adjustment control, or a plurality of select-ablyaligned eccentric spinning weights rotating in adjustable relation toone another (as in variable force pile driving technology), may be used.Furthermore, a furniture item such as a chair or bed containing anadjustable force and/or waveform vibrator or vibrators (i.e. forvibration to the backside of the patient 20, such as in treatment inacute myocardial cases) may be used as a new application for a knowntechnology. Examples of such vibrating chairs or beds, which necessarilyprovide reciprocating motion in a direction perpendicular to the longaxis of the thoracic cavity and torso in cardiac applications (such asto enable significant penetration of the vibratory signal to thestructures within the thoracic cavity) are disclosed in Canadian PatentApplication No. 2430229, PCT Application No. WO 00/67693, and JapaneseUtility Model Application No. Hei 296 133, which are incorporated hereinby reference.

For example, if no (or minimal) vibratory control is desired, then anycommercially available high powered vibratory massage or percussionsystem (i.e. providing greater than 2 mm deflections) operable underreasonable load (i.e. at least 5-10 N, and preferably at least about20-100 N), such as for example the Mini Pro 2 Thumper™, Thumper™,Homedics Professional Percussion Massager model 1 PA-1H, Sharper ImageMassager Model HF 757, OSIM Tappie, OSIM Turbo 2, OSIM iMedic Chair(i.e. for applications to the upper back region), OSIM ChiroPro (i.e.for applications to the posterior and lateral aspects of the neck), andthe “deep muscle stimulator device” as disclosed by Pivaroff in U.S.Pat. No. 6,682,496 which is incorporated herein by reference, may beused as a new application for a known technology. These devices (many ofwhich advantageously comprise, or could be easily adapted to provide-apair of contacts), typically emit one solitary high displacementamplitude stroke without a displacement amplitude regulating control,hence control of the applied forces to the body surface treated (totailor the intensity of the application to suit the tolerance level ofthe patient 20), may be achieved via use of a cloth or cushion (i.e. todampen application forces) or via a modulation of the engagement forceapplied to the vibrator against the application site. Such vibrators,(all of which tend to run exclusively on AC power cord), may bepreferably (and easily) adapted by those skilled in the art of vibrationdevice manufacture for portable battery operation to enable use in thefield (or community), wherein no AC wall outlet may be available.

Also, while the preferred embodiment (apparatus) discloses a singlemotor located within housing 14 of vibrator 10, a pair or a pluralitybeyond a pair of motors may also be used (for example, one motor foreach contact 12).

It should also be noted that there is effectively no definable maximalnor minimal limit to displacement amplitude or engagement force appliedin emergency vibration therapy (i.e. the intensity emitted is generallya function of the tolerance of the patient 20 which will vary markedly).Any of the above variations to vibration source may be therefore adaptedin size and scale to enable vibration at higher or conversely lowerloads and displacement amplitudes than what is otherwise disclosedaccording to the invention. For example, while the preferred embodimentshown (i.e. vibrator 10) provides a peak displacement amplitude of up to15 mm, this enablement is generally in excess of what is typicallyrequired, and a device limited to lower peak displacement amplitudes(i.e. with an upper limit as low as about 4-8 mm), may alternatively beemployed for satisfactory results. Lower peak displacement amplitudedevices are potentially “safer” (i.e. as the “tolerance” level of thepatient 20 may be difficult to judge at the time of treatment), andconfer lighter weight more compact systems, which are generally easierto maneuver and operate by hand. In an exemplary alternative embodiment,the vibrator employed may be operable to the maximum displacementamplitudes allowable (i.e. deemed safe) under the officiatinggovernmental regulatory body or bodies of the country wherein thevibrator is to be commercialized.

With regards to the preferred attachment interface, while the embodimentshown incorporates shaft 16 projected away from housing 14 fortransmission of vibration to contact, or preferably, contacts 12 to thepatient 20, shaft 16 is not an essential component of vibrator 10 (orprovided variant), and any transmission piece, or even the attachmentinterface itself, may be operatively linked directly to the active endof the electromechanical transducer within housing 14 of vibrator 10 (orvariant). An attachment design like that of Homedics Model PA-100massager (which incorporates a pair of electronically adjustably spacedvibration heads intimately mounted through the active end of the housingof the vibration device) is an exemplary alternative, and isincorporated herein by reference. Also, any of the aforementionedvariations to contact 12 attachment (including suction cups, a singlecontact 12, a plurality beyond a pair of contacts 12, and variantcontacts enabling ultrasonic imaging and/or LFUS wave form emissions)may be utilized solely, or in any combination, as per the methodsdescribed, to best suit the clinical situation and/or preference of theoperator.

In yet another possible embodiment of attachment, the preferred contacts12 may be replaced by a resilient nondistortable container filled with asubstantially incompressible fluid overlain with a semi-compliantmembrane (i.e. of size and shape such as to enable bridging of thesternum), wherein the vibration emitted from the active components ofvibrator 10 (or variant) may be transmitted through the incompressiblefluid and membrane and thereafter to the patient 20. The semi-compliantmembrane (which comprises the patient 20 tissue interface) is highlyresistant to longitudinal strain hence conservation of volume isachieved and vibration is efficiently transmitted. This arrangement(which enables an exacting contoured fit to the body surface treated)offers a potentially more comfortable application to the patient 20.

The engagement of the utilized vibrator (or percussion device by othername) to the selected body surface of the patient 20 may be varied inmany ways. While the embodiments shown comprises use of the hand(s) ofan operator, clamp 100 or 101 or belt 130 (and variations thereof),alternatively the employed vibration source may be engaged by means ofan upper back support of a chair (e.g. such as in the OSIM iMedic Chair,disclosed herein by reference), or stretcher (or table), wherein theselected vibrator (or percussion instrument) is housed and preferablymaneuverable within or through the upholstery of the supportive unit.

It is also possible to utilize more than one vibration device forplacement to a plurality of locations along the body of the patient 20,such as to further ensure maximal penetration and effectiveness ofvibration therapy for acute vascular disturbances. In this alternativeembodiment the vibration devices should optimally be operated in phaseto one another (i.e. to avoid potential destructive interference of thetherapeutic signal). This technique may be of particular relevancewherein an imaging technique to direct vibration therapy is notemployed.

The disclosed “dual function” ultrasonic imaging system to direct (ortarget) vibration therapy may also be embodied in a variety of ways.

For example, while the embodiment shown (apparatus) describes a direct,end to end, contact between a low frequency vibration source and anultrasonic imaging transducer (i.e. such that the ultrasonic imagingtransducer is acoustically linked to the vibration source and therebytransmits the generated low frequency vibration to the patient 20 via acommon application surface), the vibration source and ultrasonic imagingprobe may alternatively be mounted “side by side” by either a pivotassembly or an adjustable bracket (as per technology disclosed to U.S.Pat. No. 5,919,139 incorporated herein by reference), or by hand, whichin either case would reduce wear and tear on the relatively expensiveultrasonic imaging probe as the ultrasonic imaging probe itself wouldnot vibrate. The variant “by hand” technique advantageously enablesadditional manual control (or maneuverability of the ultrasonic imagingtransducer) which is generally required in ultrasonic imaging. In thisalternative “side by side vibration/imaging” embodiment, the degree oftherapeutic vibration reaching the targeted region (and thereby theoptimized placement of the vibration source or vibrator), may be gauged(or confirmed) by doppler or 2D/m mode interrogation of the invasivestructure targeted.

Furthermore, it should be understood that while an ultrasonic imagingtransducer is preferably coupled to the active components of thepreferred vibrator 10 (or alternatively the variant research vibratorfor higher frequency applications), these arrangements are not criticaland the ultrasonic imaging transducer may be coupled to any lowfrequency vibration source operable within the 1-1000 Hz range accordingto the invention (regardless of the level of provided vibratory emissioncontrol), as long as the low frequency vibration wave form emitted doesnot significantly alter or interfere with the functioning of the imagingHFUS (mega hertz) wave form. The vibration source in these cases (as thevibration emitted will be advantageously directed through a sonicpenetration window) needn't necessarily be operational at high force ordisplacement amplitudes (i.e. to ensure therapeutic penetration),however high displacement amplitude and force enablement is nonethelesspreferred in emergency situations. Such vibration sources (as statedpreviously) may comprise but should not be limited to: linear steppermotors, linear stepper motors with displacement amplification, linear(non stepper) motors, ceramic servo motors coupled to either a rotary(with cam) or linear stage, rotary motors with rotary to linearconversion elements, eccentrically spinning weights, magnetostrictiveactuators, voice coils, and shakers (e.g. with or without neodymiummagnet transducers).

As will be apparent to those skilled in the art in light of theforegoing disclosure, many alterations and modifications are possible inthe practice of this invention without departing from the spirit orscope thereof. Accordingly, the scope of the invention is to beconstrued in accordance with the substance defined by the followingclaims.

1-82. (canceled)
 83. A non-invasive vibration device adapted fordelivering a series of percussions to an external human body surfacecomprising, a) a motor which generates a series of oscillations at afrequency in the range of 1-1000 cycles per second, and b) an ultrasoundimaging transducer operatively connected to an oscillating end of saidmotor, whereby said ultrasound imaging transducer transmits said seriesof oscillations generated from said motor, and whereby said ultrasoundimaging transducer comprises a vibratory contact sized, configured anddisposed relative to said vibration device to enable operative seatingand operator controlled maneuverability within a rib-space of a humanpatient receiving said series of oscillations from said vibrationdevice, such as to enable attainment of an effective transthoracicacoustic penetration window for targeting said series of oscillationsvia a real time multidimensional image acquired by said ultrasoundimaging transducer and generated on an ultrasonic display.
 84. Thevibration device of claim 83, wherein a) said vibration device enableshand controlled maneuvering and engagement against a body surface towhich said vibration device is applied, b) said motor, once activated,linearly oscillates said ultrasound imaging transducer repeatedly at astroke length of greater than 1 mm, and wherein c) said motor isoperable under an engagement force of greater than 10 newtons.
 85. Thevibration device of claim 84, wherein said vibratory contact isoperatively sized and contoured to match the configuration of a humanrib space.
 86. The vibration device of claim 84, wherein said ultrasoundimaging transducer has an operating frequency in the 1-7 MHz range. 87.The vibration device of claim 83, wherein said vibration device enablesselective delivery of said series of percussions during the diastolicphase of a cardiac cycle.
 88. The vibration device of claim 83, whereinsaid vibration device comprises a plurality of vibratory contact-nodesspaced to enable seating to opposite sides of a bony structure upon thethorax of an individual receiving vibration from said vibration device,wherein at least one of said contact nodes comprises said ultrasonicimaging transducer.
 89. The vibration device of claim 83, furthercomprising means for emitting a therapeutic ultrasonic waveform inconcert with said series of oscillations, whereby said therapeuticultrasonic waveform comprises a lower frequency waveform that that whichis emitted from said ultrasound imaging transducer.
 90. The vibrationdevice of claim 86, wherein said motor enables successionalreciprocating motion of said ultrasonic imaging transducer while underan engagement load of greater than 10 newtons at a frequency greaterthan 20 cycles per second.
 91. The vibration device of claim 84, whereinsaid ultrasound imaging transducer comprises a phased array ultrasonicimaging transducer.
 92. A non-invasive percussion device adapted fordelivering vibration to an external body surface comprising, a) a motoroperable to generate vibration at a frequency in the range of 1-1000 Hzand a displacement amplitude in the range of 0.1-15 mm, and b) a phasedarray ultrasonic imaging transducer operatively linked to an oscillatingcomponent of said motor, whereby said phased array ultrasonic imagingtransducer transmits said vibration generated from said motor, andwhereby said phased array ultrasonic imaging transducer comprises apercussive contact sized, configured and disposed relative to saidpercussion device to enable operative seating and operator controlledmaneuverability within a rib-space of a human patient receiving saidvibration from said percussion device, such as to enable attainment ofan effective transthoracic acoustic penetration window for targetingsaid vibration via a real time multidimensional image acquired by saidphased array ultrasonic imaging transducer and generated on anultrasonic display.
 93. The percussion device of claim 92 wherein saidpercussion device, once activated to oscillate, oscillates said phasedarray ultrasonic imaging transducer repeatedly at a displacementamplitude of greater than 1 mm.
 94. The percussion device of claim 92wherein said motor is disposed within a housing sized and configured toenable hand controlled maneuvering and engagement of said percussiondevice, wherein said phased array ultrasonic imaging transducer isprojected from said housing, such as to enable contact of said phasedarray imaging transducer against a body surface to which said percussiondevice is applied.
 95. The percussion device of claim 94, wherein saidmotor, once activated to oscillate, generates a series of oscillationsand thereby repeatedly oscillates said phased array ultrasonic imagingtransducer at a frequency greater than 20 cycles per second
 96. Thepercussion device of claim 95, wherein said percussion device has atleast one percussive contact interface sized such that the majority ofsaid contact interface enables seating between two opposing ribs of ahuman rib space.
 97. The percussion device of claim 96, wherein saidpercussion device has at least one percussive attachment interfaceoperatively configured to match the contour and size of a human ribspace.
 98. The percussion device of claim 95, wherein said phased arrayultrasonic imaging transducer has an operating frequency in the 1-7 MHzrange.
 99. A method using the vibration device as defined in claim 1 fortreatment of a state of low blood perfusion within an individual,comprising the steps of: a) locating an application site for saidvibration device upon a non-invasive external body surface of saidindividual via use of an image acquired by said ultrasonic imagingtransducer of said vibration device, and b) applying a series ofoscillations at a frequency in the range of 1-1000 Hz and a displacementamplitude in the range of 0.1-15 mm via transmission through saidultrasonic imaging transducer upon said application site to remediatesaid state of low blood perfusion, whereby said image represents auseful target for said series of oscillations.
 100. The method of claim99, wherein said ultrasonic imaging transducer comprises a phased arrayultrasonic imaging transducer.
 101. The method of claim 99, wherein saidstate of low blood perfusion comprises an acute thrombotic arterialobstruction.
 102. A method for using non-invasively delivered percussionin treatment of a blood flow disorder in a patient, comprising the stepsof: a) obtaining an ultrasonic image by placing an ultrasonic imagingtransducer in contact with a non-invasive application site of saidpatient, said image representing a target for said percussion, and b)applying percussion at a frequency in the range of 1-1000 Hz and adisplacement amplitude in the range of 0.1-15 mm upon said applicationsite in order to remediate said blood flow disorder.
 103. The method ofclaim 102, wherein said blood flow disorder comprises at least one of ablood flow disorder of the heart and a blood flow disorder of the lung.104. A hand held non invasive vibrator adapted for enabling imagingguided vibration to a space between the ribs of a patient, comprising a)a motor operable at engagement forces greater than 10 newtons, which isadministrable to generate vibration at a frequency of greater than 20 Hzand less than 1000 Hz, said motor disposed within a housing adapted toenable hand held positional control and engagement of said vibrator, andb) an ultrasonic imaging transducer mechanically linked to an activeoscillating end of said motor and projected from said housing, saidultrasonic imaging transducer comprising a vibratory patient contactwith a contact surface sized, shaped, configured, and disposed relativeto said vibrator to enable operative seating and operator controlledmaneuverability within a rib space of a human patient receivingvibration from said vibrator, whereby, said motor linearly oscillatessaid vibratory patient contact towards said space between the ribs ofsaid patient to which said vibrator is applied, such as to enable handcontrolled engagement and targeting of said vibration through a humanrib-space via an ultrasonic image acquired by said ultrasonic imagingtransducer and generated on an ultrasonic display.
 105. The vibrator ofclaim 104, wherein said motor is administrable to generate vibration ata displacement amplitude of at least 1 mm.
 106. The vibrator of claim105, wherein said ultrasonic imaging transducer has an operatingfrequency in the 1-7 MHz range.
 107. The vibrator of claim 106, whereinsaid ultrasonic imaging transducer comprises a phased array ultrasonicimaging transducer.